Shape memory polymer intraocular lenses

ABSTRACT

A shape memory polymer (SMP) intraocular lens may have a refractive index above 1.45, a Tg between 10° C. and 60° C., inclusive, de minimis or an absence of glistening, and substantially 100% transmissivity of light in the visible spectrum. The intraocular lens is then rolled at a temperature above Tg of the SMP material. The intraocular device is radially compressed within a die to a diameter of less than or equal to 1.8 mm while maintaining the temperature above Tg. The compressed intraocular lens device may be inserted through an incision less than 2 mm wide in a cornea or sclera or other anatomical structure. The lens can be inserted into the capsular bag, the ciliary sulcus, or other cavity through the incision. The SMP can substantially achieve refractive index values of greater than or equal to 1.45

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 13/441,754, filed on 6 Apr. 2012, which is a continuation ofU.S. patent application Ser. No. 13/500,884, filed 6 Apr. 2012, which isa national stage entry under 35 U.S.C. §371 off International PatentApplication No. PCT/US2012/028150, filed on 7 Mar. 2012, which claimsthe benefit of priority pursuant to 35 U.S.C. §119(e) of U.S.provisional application No. 61/449,865 filed 7 Mar. 2011 entitled “Shapememory polymer intraocular lenses” and U.S. provisional application No.61/474,696 filed 12 Apr. 2011 entitled “Shape memory polymer intraocularlenses,” all of which are hereby incorporated herein by reference intheir entirety.

TECHNICAL FIELD

The technology described herein relates to artificial intraocularlenses.

BACKGROUND

The human eye functions to provide vision by transmitting light througha clear outer portion called the cornea, and focusing the image by wayof a crystalline lens onto a retina. The quality of the focused imagedepends on many factors including the size and shape of the eye, and thetransparency of the cornea and the lens.

When age or disease causes the lens to become less transparent, visiondeteriorates because of the diminished light which can be transmitted tothe retina. This deficiency in the lens of the eye is medically known asa cataract. An accepted treatment for this condition is surgical removalof the lens and replacement of the lens function by an artificialintraocular lens (IOL).

Intraocular lenses are employed as replacements for the crystalline lensafter either extracapsular or intracapsular surgery for the removal of acataract. In the United States, the majority of cataractous lenses areremoved by a surgical technique called phacoemulsification. During thisprocedure, an opening is made in the anterior capsule and a thinphacoemulsification cutting tip is inserted into the diseased lens andvibrated ultrasonically. The vibrating cutting tip liquefies oremulsifies the lens so that the lens may be aspirated out of the eye.The diseased lens, once removed, is replaced by an artificial lens.

Intraocular lenses are generally of two types, those that are placed inthe anterior chamber, i.e., between the iris and the cornea, and thosethat are placed in the posterior chamber, i.e., behind the iris. Bothtypes of lenses are conventionally employed with the choice between ananterior chamber and a posterior chamber lens being partly dictated byrequirements of the patient and partly dictated by the preferences ofthe physician inserting the lens. A third type of lens, known asiris-fixated lenses because they are secured to the iris periphery, canbe thought of as being within one of the two types above, in that theiroptic portion is in either the anterior or posterior chamber.

Intraocular lenses normally consist of an optic with at least one andpreferably two or more haptics that extend generally radially from theoptic and contain distal portions that normally seat in the scleral spurfor an anterior chamber lens and either in the ciliary sulcus or withinthe lens capsule for a posterior chamber lens. The optic normallycomprises a circular transparent optical lens. The haptic in most lensesis a flexible fiber or filament having a proximate end affixed to thelens and having a distal end extending radially away from the peripheryof the lens to form a seating foot. Several haptic designs are currentlyin use, for example, a pair of C-shaped loops in which both ends of eachloop are connected to the lens, and, for example, J-shaped loops inwhich only one end of the loop is affixed to the lens.

Haptics are usually radially resilient and extend outwardly from theperiphery of the lens and gently, but elastically, engage appropriatecircumferential eye structures adjacent the iris or within the capsularbag. This resiliency is due to the conventional elastic properties ofthe materials of the haptic. The result is a haptic which whencompressed and released will uncontrollably spring back immediately.This property makes the process of implantation and final positioning ofthe lens difficult since the haptics must be constrained duringimplantation. Also, once situated, the flexibility of the conventionalhaptic material makes the lens susceptible to decentration from beingpushed by vitreous pressure from behind the lens or shifting due topressure from adjacent ocular tissue. Also, the forces generated by theelastic recoil of the haptic release may damage the delicate localtissue.

The optimum position for a posterior chamber lens is in the capsularbag. This is an extremely difficult maneuver for the surgeon toaccomplish. When a posterior chamber lens is employed it must be placedthrough the small pupillary opening, and the final haptic position ishidden behind the iris and not visible to the surgeon. It is thereforehighly desirable to keep the overall dimensions of the posterior chamberlens as small as possible during implantation, letting it expand when itis finally situated where the surgeon intends, usually in the capsularbag. A small device is easier to manipulate in the eye, reduces thechance of the haptics coming in contact with the corneal endothelialtissue, and allows the surgeon ease of insertion, as he must ofteninsert a lens with a 14 mm overall dimension through a pupil of 5 to 8mm diameter. A smaller lens also reduces the lens/iris contact and canbetter guarantee that the intraocular lens and its haptics will be inthe capsular bag.

In recent years intraocular lenses with and without haptics havingrelatively soft body portions have been provided such that the bodyportion could be folded generally across the diameter thereof forinsertion into a smaller opening during implantation of the lens. Lensesformed of liquid or hydrogel constrained within a sheath have beendesigned which allow the lens body to be folded before insertion andthen subsequently filled when in position. Unfortunately, the softmaterials used for the bodies of these lenses lack the restorativestrength sometimes required to return to their original shape.

Further, these lens types are typically deployed using either an elasticrelease mechanism, wherein mechanical energy stored by bending theelastic material is released when the mechanical constraint is removed,or through water uptake, also known as hydration, wherein the lensgradually absorbs water through an osmotic diffusion process. Bothprocesses are difficult to control. In the former case, the elasticrecoil may damage local tissue or may move the lens away from thecenter. In the latter case, the ultimate shape of the lens may becomedistorted if the expanding lens comes into contact with surroundingtissue. Further, hydrating materials are known to possess poor shaperecovery properties.

In the natural lens, bifocality of distance and near vision is providedby a mechanism known as accommodation. The natural lens, early in life,is soft and contained within the capsular bag. The bag is suspended fromthe ciliary muscle by the zonules. Relaxation of the ciliary muscletightens the zonules, and stretches the capsular bag. As a result, thenatural lens tends to flatten. Tightening of the ciliary muscle relaxesthe tension on the zonules, allowing the capsular bag and the naturallens to assume a more rounded shape. In this way, the natural lens canbe focused alternatively on near and far objects. As the lens ages, italso becomes harder and is less able to change shape in reaction to thetightening of the ciliary muscle. This makes it harder for the lens tofocus on near objects—a medical condition known as presbyopia.Presbyopia affects nearly all adults over the age of 45 or 50.

Typically, when a cataract or other disease requires the removal of thenatural lens and replacement with an artificial IOL, the IOL is amonofocal lens, requiring that the patient use a pair of spectacles orcontact lenses for near vision. Some bifocal IOLs have been created, butare not been widely accepted. Some IOL designs are single optic lenseshaving flexible haptics that allow the optic to move forward andbackward in reaction to movement of the ciliary muscle. However, theamount of movement of the optic in these single-lens systems may beinsufficient to allow for a useful range of accommodation. In addition,the eye must be medicated for one to two weeks to decrease eye movementin order for capsular fibrosis to entrap the lens that thereby providefor a rigid association between the lens and the capsular bag. Further,the commercial models of these lenses are made from a hydrogel orsilicone material. Such materials are not resistive to the formation ofposterior capsule opacification (“PCO”). The treatment for PCO is acapsulotomy using a Nd:YAG laser that vaporizes a portion of theposterior capsule. Such destruction of the posterior capsule may destroythe mechanism of accommodation of these lenses.

Known accommodative lenses also lack extended depth of focus in additionto having poor accommodation performance. Such known lenses furtherrequire precise lens sizing for proper function over a range of capsularbag sizes and lack long-term capsular fixation and stability. Further,as current lens replacement surgeries move towards smaller incisionsize, IOLs in general require the ability to be delivered through suchsmall incisions.

Dual-optic lenses leverage the ability of the ciliary body-zonulecomplex to change the shape of the capsular bag. This allows theinter-lens distance to change, thereby allowing a change in refractiveerror. These dual-optic lenses can be large secondary to the opticalhardware needed to create this optical system and requires largercorneal incisions to insert into the eye.

Intracorneal lenses are designed to treat refractive error orpresbyopia. Intracorneal lenses include corneal implants and lenses,which are inserted through a small incision in the cornea created by ablade or a laser. The pocket formed by the incision in the cornea isused to position the implant to change the shape of the cornea. In thecase of a lens implant, the pocket is used to position the refractivelens in the optically effective location. Some lenses create apinhole-type effect to treat presbyopia. As current intraocorneal lensesmove towards smaller incision size, devices in general require theability to be delivered through such small incisions. Laser technologysuch as the femtosecond laser has enhanced the ability to create thesesmaller corneal wounds and pockets for implantation.

Phakic intraocular lenses are implanted either in the anterior chambersupported by the angle structures or in the posterior sulcus immediatelyposterior to the iris and anterior to the native lens. The lens isimplanted through a minimally invasive wound at the limbus and insertedinto or through the anterior chamber. The lenses are used to treatrefractive error and have the risk of causing trauma to the lens and/orangle structures. Smaller incisions require folding the lens and thenlens deployment in the eye, which increases the risk of damage tointraocular structures.

Known acrylic lens materials are unable to be compressed significantlyto achieve desired functionality for IOLs. While various methodologiesare known to fold or roll acrylic IOLs, these merely address the need toreduce the form factor of a deployed shape for the purposes ofminimizing the required incision size for implantation. The actualvolume displaced by these lenses remains constant so there is a limit onthe minimum size that such IOLs can reach. Further, the ability to foldor roll these IOLs is limited by the ability of the material to resiststrain caused by the stress of folding and return to a desired shape andprovide the necessary optical qualities after implantation. Further,there is little control over the speed and force with which deploymentof a lens occurs once it is implanted, which often causes trauma totissues which engage haptics of the IOL.

The information included in this Background section of thespecification, including any references cited herein and any descriptionor discussion thereof is included for technical reference purposes onlyand is not to be regarded subject matter by which the scope of theinvention as defined in the claims is to be bound.

SUMMARY

Shape-memory polymers (SMP) are a class of smart materials that can betailored to have significant mechanical property changes in response toa given stimulus. The ability to recover from large deformations andadapt to differing environmental conditions greatly facilitates use ofSMP devices in minimally invasive surgery. Current shape memory polymerformulations can be created to have independently programmed modulus andglass transition temperatures (Tg). The ability to precisely controlmechanical properties of SMP along with the transparent nature of thematerial, a refractive index in ranges very similar to the range of ahuman lens (1.386-1.406 and greater), and proven biocompatibility allowsfor the creation of unique solutions for treatment of various ophthalmicdiseases. Therefore, there are many aspects of a hydrophobic,acrylate-based, SMP intraocular lens which are appealing in view ofother lens options.

One clear advantage of the SMP systems disclosed herein is the dramaticcapability to vary mechanical properties by changing material propertiessuch as cross-linked weight percentage, fractions of each componentco-monomer, and other ingredient properties. This provides thecapability to design the required mechanical properties for the specificapplication into the material. For example, varying Tg for particularSMP formulations affects resultant rubbery modulus. Additional propertychanges can be incorporated, for example, by varying the weightpercentage of the co-monomers forming the SMP. The SMP materialqualities may also be leveraged to change the radius of curvature of theanterior and posterior surfaces of particular IOL designs with heat, UVlight, or other processes to change the central and/or paracentral powerof the particular lens.

A variety of intraocular lenses may be formed of a shape memory polymerwith high degrees of “shape certainty” or “shape-fixity” (i.e., theaccuracy of the recovered shape after transition from the deformed shapeback to the permanent shape). The lenses are deformed and compressedinto a compact preoperative shape that allows for implantation through asmall incision, gently unfurl and expand into guaranteed post-operativeshapes (permanent shapes), and provide an integrated haptic for a stableand nontraumatic apposition to ciliary sulcus, capsular bag, or anteriorchamber angle structures. The SMP lenses may be deformed and compressedto sizes smaller than currently known and available for implantationthrough an incision size under 2 mm, which is currently the lower limit.

In one exemplary implementation, a method of manufacturing anintraocular device includes providing a shape memory polymer (SMP)material with a Tg, forming the SMP material in a permanent intraoculardevice form, mechanically compressing the intraocular device at atemperature above Tg to deform the intraocular device into a smallervolume; and cooling the deformed intraocular device while still incompression to a temperature below Tg to thereby create a stabledeformed intraocular device with a delivery profile allowing forinsertion through an incision of 2 mm or less. In one embodiment, theintraocular device may be rolled at a temperature above Tg of the SMPmaterial. The rolled intraocular device may then be cooled while stillin a rolled form to a temperature below Tg to thereby create a stablerolled intraocular device. The intraocular device may then bemechanically compressed to a diameter of less than 1.8 mm. In anotherembodiment, the intraocular device may be rolled at a temperature aboveTg of the SMP material. The intraocular device may then be radiallycompressed within a die to a diameter of less than 1.8 mm whilemaintaining the temperature above Tg.

In another exemplary implementation, a shape memory polymer (SMP)intraocular lens may have a refractive index above 1.45, a Tg between15° C. and 40° C., inclusive, de minimis or an absence of glistening,and substantially 100% transmissivity of light in the visible spectrum.In one embodiment, the SMP intraocular lens may be formed of acombination of 50 weight percent tBA, 28 weight percent isobutylacrylate, and 22 weight percent PEGDMA 1000. In another embodiment, theSMP intraocular lens may be formed of a combination of 22 weight percenttBA and 78 weight percent PEGDMA 1000. In a further embodiment, the SMPintraocular lens may be formed of a combination of 65 weight percenttBA, 13 weight percent butyl acrylate, and 22 weight percent PEGDMA1000.

In another exemplary implementation, a shape memory polymer (SMP), suchas in an IOL, may be derived from a formulation comprising: tertbutylacrylate (tBA); one or more poly(ethylene glycol) dimethacrylate(PEGDMA) monomers; optionally one or more UV-blockers; optionally one ormore polymerization initiators; optionally n-butyl acrylate (nBA); andoptionally 2-hydroxy-3-phenoxypropyl acrylate (HPPA). The SMP may bederived from a formulation comprising 50-85 wt % tBA. The SMP may bederived from a formulation comprising 0.25-25 wt % PEGDMA, 0.5-25 wt %PEGDMA, or 3-25 wt % PEGDMA. The SMP may be derived from a formulationcomprising 0-1.5 wt % UV-blockers, or 0.25-1.5 wt % UV-blockers. The SMPmay be derived from a formulation comprising 0-3.0 wt % polymerizationinitiators, or 0.05-3.0 wt % polymerization initiators. The SMP may bederived from a formulation comprising 0-20 wt % nBA. The SMP may bederived from a formulation comprising 0-20 wt % HPPA. The SMP may bederived from a formulation comprising 50-85 wt % tBA; 3-25 wt % PEGDMA;0.25-1.5 wt % UV-blockers; 0.05-3.0 wt % polymerization initiators; 0-20wt % nBA; and 0-20 wt % HPPA.

The PEGDMA may be selected from the group consisting of: PEGDMA 550;PEGDMA 750; PEGDMA 1000; and PEGDMA 2000; or any combination thereof.The PEGDMA may be PEGDMA 750. The PEGDMA may be PEGDMA 1000.

The one or more UV-blockers may be selected from the group consistingof: a methacryloyl chlorobenzotriazole; a methacryloylmethoxybenzotriazole; and a yellow dye; or any combination thereof. TheUV-blocker may be selected from the group consisting of: 2-methylacrylicacid3-[3-tert-butyl-5-(5-chlorobenzotriazol-2-yl)-4-hydroxyphenyl]-propylester (UVB); and2-(2-hydroxy-3-tert-butyl-5-vinylphenyl)-5-chloro-2H-benzotriazole(UVAM). The UV-blocker may be3-(tert-butyl)-4-hydroxy-5-(5-methoxy-2H-benzo[d][1,2,3]triazol-2-yl)phenethylmethacrylate.

The one or more polymerization initiators may be selected from the groupconsisting of: 2,2-dimethoxy-2-phenylacetophenone (Irgacure 651);phenylbis(2,4,6-trimethylbenzoyl) phosphine oxide (Irgacure 819);azobisisobutyronitrile (AIBN); lauroyl peroxide;di(4-tert-butylcyclohexyl) peroxydicarbonate (Perkadox 16);camphorquinone; and diphenyl-(2,4,6-trimethylbenzoyl)-phosphine oxide(TPO); or any combination thereof. The polymerization initiator may belauroyl peroxide. The polymerization initiator may include a photoinitiator and a thermal initiator.

The shape memory polymer material may be derived from a formulationselected from the group consisting of SMP 208, SMP209, SMP210, SMP211,SMP213, SMP214, SMP215, SMP218, SMP219, and SMP230b, wherein SMP208comprises tBA (77.5%), UVB (0.5%), PEGDMA1000 (22%), and IRGACURE819(0.15%); SMP209 comprises tBA (77.0%), UVB (1.0%), PEGDMA1000 (22%), andIRGACURE819 (0.15%); SMP210 comprises tBA (76.0%), UVB (2.0%),PEGDMA1000 (22%), and IRGACURE819 (0.15%); SMP211 comprises tBA (77.5%),UVAM (0.5%), PEGDMA000 (22%), and IRGACURE819 (0.15%); SMP212 comprisestBA (77.0%), UVAM (1.0%), PEGDMA1000 (22%), and IRGACURE819 (0.15%);SMP213 comprises tBA (76.0%), UVAM (2.0%), PEGDMA1000 (22%), andIRGACURE819 (0.15%); SMP214 comprises tBA (77.3%), UVB (0.7%), PEGDMA000(22%), and IRGACURE819 (0.15%); SMP215 comprises tBA (77.45%), UVAM(0.55%), PEGDMA1000 (22%), and IRGACURE819 (0.15%); SMP218 comprises tBA(6430%), nBA (13.0%), UVB (0.7%), PEGDMA1000 (22%), and IRGACURE819(0.15%); SMP219 comprises tBA (64.45%), nBA (13.0%), UVAM (0.55%),PEGDMA1000 (22%), and IRGACURE819 (0.15%); and SMP230b comprises tBA(59.80%), nBA (12.00%), UVB (0.80%), PEGDMA1000 (10%), lauroyl peroxide(0.15%), and HPPA (17.50%); wherein UVB is 2-methylacrylic acid3-[3-tert-butyl-5-(5-chlorobenzotriazol-2-yl)-4-hydroxyphenyl]-propylester; UVAM is2-(2-hydroxy-3-tert-butyl-5-vinylphenyl)-5-chloro-2H-benzotriazole(UVAM); and IRGACURE819 is phenylbis(2,4,6-trimethylbenzoyl) phosphineoxide. The shape memory polymer material may be derived from aformulation comprising: 59.80 wt % tBA; 12.00 wt % nBA; 17.50 wt % HPPA;0.70 wt % 2-methylacrylic acid3-[3-tert-butyl-5-(5-chlorobenzotriazol-2-yl)-4-hydroxyphenyl]-propylester (UVB); 10 wt % PEGDMA 1000; and 0.15 wt % lauroyl peroxide.

An intraocular lens comprising the shape memory polymer material mayhave a refractive index above 1.45; a Tg between 10° C. and 60° C.,inclusive; de minimis or an absence of glistening; and substantially100% transmissivity of light in the visible spectrum.

In another exemplary implementation, a shape memory polymer (SMP), suchas in an IOL, may be derived from a formulation comprising: tertbutylacrylate (tBA); one or more poly(ethylene glycol) dimethacrylate(PEGDMA) monomers; optionally n-butyl acrylate (nBA); and optionally2-hydroxy-3-phenoxypropyl acrylate (HPPA).

In a further exemplary implementation, a method of implanting anintraocular lens device includes making an incision in a cornea orsclera less than 2 mm wide. In one embodiment, an intraocular lens isinserted into the capsular bag through the incision. In anotherembodiment, an intraocular lens is inserted into the ciliary sulcusthrough the incision. In another embodiment, a method of implanting anintraocular lens device includes making an incision into a cornea lessthan 2 mm wide to access the anterior chamber. An intraocular lens isthen inserted into the anterior chamber through the incision. In afurther embodiment, a method of implanting an intracorneal implantdevice includes making an incision into a cornea less than 2 mm wide tocreate a tunnel in the cornea. An intracorneal implant device is theninserted into the anterior chamber through the incision.

This Summary is provided to introduce a selection of concepts in asimplified form that are further described below in the DetailedDescription. This Summary is not intended to identify key features oressential features of the claimed subject matter, nor is it intended tobe used to limit the scope of the claimed subject matter. A moreextensive presentation of features, details, utilities, and advantagesof the present invention as defined in the claims is provided in thefollowing written description of various embodiments of the inventionand illustrated in the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph depicting the storage modulus vs. temperatureattributes for several exemplary SMP formulations.

FIG. 2 is a graph depicting the UV blocking properties and opticalclarity of the exemplary SMP formulations of FIG. 9 as a percentage oftransmission over a range of wavelengths in the UV and visible spectrum.

FIG. 3 is a graph depicting the storage modulus vs. temperatureattributes for several exemplary SMP formulations.

FIG. 4 is a graph depicting the UV blocking properties and opticalclarity of the exemplary SMP formulations of FIG. 11 as a percentage oftransmission over a range of wavelengths in the UV and visible spectrum.

FIG. 5 is a graph depicting the compression properties of the exemplarySMP formulations of FIG. 11.

FIG. 6 is a graph depicting the tensile properties of an exemplary SMPformulation at two different rates of strain.

FIG. 7 is an optical profilometry image of a sample SMP IOL lens surfaceshowing average surface roughness.

FIG. 8A is an isometric view of an exemplary shape memory polymer (SMP)intraocular lens (IOL) with placement haptics in a permanent or deployedconfiguration.

FIG. 8B is a top plan view of the SMP IOL of FIG. 1A.

FIG. 8C is a front elevation view of the SMP IOL of FIG. 1A.

FIG. 8D is a side elevation view of the SMP IOL of FIG. 1A.

FIG. 9A is a top plan view of an exemplary SMP IOL placed on a rollingdie with a channel for rolling the SMP IOL.

FIG. 9B is a front elevation view of the rolling die of FIG. 2A with theSMP IOL folded into the channel under compression by a wire runningaxially down the channel.

FIG. 10A is a schematic front elevation view of the rolling die of FIG.2A with the edges of the SMP IOL folded over and the rolling die cooledbelow Tg.

FIG. 10B is a schematic elevation view of the SMP IOL removed from therolling die and maintaining a deformed, rolled configuration.

FIG. 11 is a schematic diagram of the rolled SMP IOL placed in a fabricsock.

FIG. 12A is a top plan view, in cross section of the SMP IOL within thefabric sock being pulled through a tube of decreasing diameter formed ina compression die heated above Tg.

FIG. 12B is a is a top plan view, in cross section of the SMP IOL withinthe fabric sock compressed within the smallest diameter section of thetube while the compression die is cooled below Tg.

FIG. 13 is a schematic elevation view of the SMP IOL removed from thecompression die and sock maintaining a deformed, rolled, extended, andradially compressed configuration.

FIG. 14A is a schematic top plan view of a folding and compression toolused to fold a SMP IOL in conjunction with a temperature-regulatedcompression system.

FIG. 14B is a schematic side elevation view in cross section of the toolof FIG. 7A used in conjunction with a temperature-regulated compressiontool.

FIG. 14C is a schematic side elevation view in cross section of thefolding and compression tool in a compressed position with thetemperature-regulated compression tool.

FIG. 15 is a picture of a polymer slide with a coupon cutting diagramoverlayed.

FIG. 16 is a transmission spectrum of SMP 214, 215, 218, and 219 (1.0 mmthick).

FIG. 17 is a transmission spectrum of SMP230b (0.7 mm thick and 1.4 mmthick).

DETAILED DESCRIPTION

The SMP IOLs disclosed herein are more deformable than known acryliclens materials (in some cases greater than 65% compression and greaterthan 250% tensile strain) and thus the volume displaced by such devicescan actually be reduced for implantation. This allows for implantationthrough reduced incision sizes (sub 2 mm and even sub 1.8 mm) and thusreduced trauma to the human eye. Several other benefits are alsoachievable by using SMP IOLs disclosed herein.

The refractive index of many of the formulations (n₀≈1.464) isrelatively high (higher than the refractive index of human lens tissue)and thus allows for the possibility of reducing the thickness of thelens and therefore of the size of the delivery profile. The refractiveindex of SMP IOLs can further be modified by formulation of the SMPmaterial.

The formulations of the SMP materials can be adjusted to slow or timedelay the shape recovery process in order to reduce trauma to tissue inthe implant location and to allow the surgeon adequate time formanipulation and placement of the IOL in the proper location. With someSMP formulations, post implant modification is possible, e.g., to changethe curvature of the optic or the index of refraction. This may berealized through application of non-intrusive heating of the SMP IOL, orportions thereof post-implant via laser or ultrasound. Such heating maybe applied to particular sections of the SMP IOL which have differentcross-link weight percentages of material (and thus different Tg inthose areas) to allow activation of a secondary or tertiary shapechange, which may be used to effect changes to the refractive index, thecurvature of the optic, or the expansion of the haptics. For example,the configuration of the haptic-optic junction may be changed to modifythe vault of the optic by heating the junction. Such secondary ortertiary shape changes may also be used to promote interaction with thelens capsule, vitreous, zonules and surrounding tissues to help inaccommodation. In addition, the baseline positioning of the two opticsin a dual optic accommodative intraocular lens system can be changedeven after implantation.

The SMP materials may provide extremely high shape fixity (>95-99%). Thehigher the shape fixity, defined as the percent change in recoveredshape compared to the original molded shape, the higher thereproducibility and confidence that the deployed IOL will function asintended (e.g., the post deployment shape of IOLs should be highlycontrolled to maximize the optical characteristics of the device). TheSMP materials disclosed herein provide extremely high shape fixity inlarge part because the SMP materials deploy using a non-elastic,non-melt shape recovery process (i.e., it is not a phase change usingfluid properties). Further, the SMP materials are not a hydrogel orother type of hydrating material. The SMP materials transform from onehighly-reproducible, non-changing, non-creeping, non-deforming, storageshape, to another highly-reproducible, non-changing, non-creeping,non-deforming, secondary (permanent) shape.

The SMP materials may have a pre-programmed shape; and post-deploymentthe SMP devices release internal stored energy to move to the programmedshape, which may or may not be adaptive to the local tissue. The localtissue does not play a part in shaping the form of the SMP devices. TheSMP devices return to their “permanent” shape as originally formed whenmolded, before being deformed for smaller profile delivery. The speed offull deployment from the deformed state to the glass (permanent) statecan be varied over a wide range from less than a second to over 600seconds depending upon the SMP formulation.

The disclosed high Tg (i.e., at or above body temperature) SMPformulations provide for processes of packaging, shipping, storing, andultimately implanting SMP devices that do not require refrigeratedstorage or ice or an otherwise low-temperature operating environment.Thus, a significant advantage of the SMP materials described herein isthat they can be stored in the stored shape for extended periods oftime, they can be packaged in constrained forms within a customizeddelivery system, and they can be deployed without need for priorrefrigeration or other temperature changes. For example, during shippingof a device, the environmental effect of cycling of temperatures andinadvertent deployment of a device can be eliminated by constraining thedevice in a delivery system or packaging system.

Optionally, SMP IOL formulations disclosed herein may include (e.g., beimpregnated with) various drugs that may be eluted from the SMP IOL onceimplanted in vivo to assist with the healing process of the opticaltissue traumatized during implantation or to deliver therapeuticmedications to treat other ocular diseases. The medication or activeingredient (e.g., a biologic agent) may be integrated into the SMP IOLas part of the polymerization process, within a swelling agent (e.g., asa chemical or physical hydrogel polymer structure), or as abiodegradeable, drug-eluting polymer portion of the final SMP IOLdevice. Exemplary drugs that may be impregnated in the SMP IOL mayinclude antibiotics, anti-inflammatories, anti-histamines, anti-allergy,biologic agents (e.g., anti-VEGF agents, siRNAs, etc), and glaucomamedications (i.e., medications to decrease eye pressure, which include,but are not limited to, prostaglandins,parasympathetic/sympathetic-based medications, alpha agonists, betablockers, carbonic anhydrase inhibitors, Rho Kinase inhibitors,adenosine agonists, endothelin agonists and antagonists, etc). Otheragents that may be linked to an SMP IOL include viral vectors andcell-based therapeutics.

A variety of intraocular lens types can be made of SMP materialsaccording to the formulations described below, having selected materialproperties to meet the needs of the particular lens type or design.Several of these lens options are also described below.

Shape Memory Polymer Materials

The SMP formulations disclosed herein allow IOLs to be created to meetspecific design requirements. Further, the SMP formulations allow IOLsto be manufactured using scalable liquid injection manufacturingtechniques. The SMP formulations disclosed herein can provide IOLs withthe following advantageous properties: shape fixity of >98.5%; recoveryrates of between 0.25 seconds to 600 seconds, including clinicallydesirable rates of between 3 and 25 seconds, inclusive; minimum devicedeformations of at least 40%0 in any dimension during the manufacturingprocess, and preferentially of 100-200%; rubbery modulus of 250 kPa to20,000 kPa; tailoring of Tg for folding, compression, and injection;glistening-free (an industry term describing optical imperfectionspossible in polymer formulations for intraocular lenses); UV blockingcapabilities; coloration of blue, yellow, red, and green, orcombinations thereof; cycle times for liquid injection manufacturing of30 seconds to 20 minutes; ability to tolerate high temperaturemold-based manufacturing, e.g., temperatures of as much as 400 degrees;capability to tolerate high-pressure mold-based manufacturing,specifically pressures of as much as 50 Mpa; ability to flow throughextremely narrow channels (<100 microns diameter) during the mold-basedmanufacturing process (i.e., low viscosity at manufacturingtemperatures); and volume shrinkage to permanent shape of 3%-15% or lessafter thermal curing in the mold-based manufacturing process.

SMP materials have significant capacity to change shape or otherwiseactivate with a mechanical force in response to an external stimulus.The stimulus may be light, heat, chemical, or other types of energy orstimuli. The thermomechanical response of SMP materials may becontrolled through formulation to predict and optimize shape-memoryproperties. Shape memory polymer devices may be designed and optimizedto a high degree of tailorability that are capable of adapting andresponding to particular biomedical applications and patient physiology.

A polymer may be considered a SMP if the original shape of the polymercan be deformed and remain stable in the deformed state until acted uponby an external stimulus, and then the original shape can be recovered byexposing the material to the appropriate stimulus. In oneimplementation, the stimulus may be heat. The original shape may be setby molding, extruding, stamping, or other typical polymer processingprocesses. In addition, a disc, rod, or other configuration of thematerial may be formed by the above processes and then shaped into afinal shape with cryolathing, which is a process involving freezing ofthe material followed by laser and/or mechanical cutting of the materialinto a final shape. The temporary shape may be set by thermo-mechanicaldeformation. Heating the deformed SMP material above a shape deformationrecovery temperature results in recovery of the original shape, even ifthe original molded shape of the polymer is altered mechanically at alower temperature than the deformation recovery temperature. SMPmaterials disclosed for use in the applications herein have the abilityto recover large deformation upon heating and in appropriateformulations with greater than 99% accuracy of the original shape.

In one implementation using heat stimulus, a polymer transitiontemperature may be tailored to provide for a deformation recoverytemperature, at body temperature, about 37° C.; i.e., the glasstransition temperature, Tg, of the polymer is designed to be about 37°C. The distinct advantage of this approach is the utilization of thethermal energy of the human body to naturally activate the SMP material.For some applications, the mechanical properties (e.g., stiffness) ofthe material are strongly dependent on Tg. Thus, it may be difficult todesign an extremely stiff device when Tg is close to the bodytemperature due to the compliant nature of the polymer. Anotherconsideration in medical applications is that the required storagetemperature of a shape memory polymer with Tg about 37° C. willtypically be below room temperature requiring “cold” storage beforedeployment. In higher temperature transportation or storageenvironments, the folded shape may be retained through the use of aconstraining device which does not allow the device to deploy into itsinitially molded shape.

In an alternative implementation, the recovery temperature is higherthan the body temperature, i.e., Tg>37° C. The advantage of thisimplementation is that the storage temperature can be equal to roomtemperature facilitating easy storage of the device and avoidingunwanted deployments before use. The folded shape may be retainedthrough the use of a constraining device which does not allow the deviceto deploy into its initially molded shape. However, local heating of thematerial upon deployment may be needed to induce recovery of the SMPmaterial. Local damage to some tissues in the human body may occur attemperatures approximately 5 degrees above the body temperature througha variety of mechanisms including apoptosis and protein denaturing.Local heating bursts may be used to minimize exposure to elevatedtemperatures and circumvent tissue damage. The use of one method overthe other is a design decision that depends on the targeted body systemand other device design constraints such as required in-vivo mechanicalproperties.

In order to deliver the IOLs through the smallest possible incision, themechanical properties of the SMP devices may be developed to achievehigh levels of recoverable strain. In tension, up to 180% strain can beachieved for 10% cross-linked systems and up to 60% strain can beachieved in 40% cross-linked systems. In compression 80% or more straincan be achieved with the above percentage cross-link. The desired levelsof strain in tension and compression are determined by the level ofdeformation required to fit the SMP IOL into the delivery system.Formulations with lower amounts of cross-linking can undergo higherlevels of deformation without failure. Current IOLs utilize 5%-40%cross-linking to achieve the material properties for the desired levelof recoverable strain.

The SMP IOLs and SMP materials may have a refractive index of 1.45 orgreater, 1.46 or greater, 1.47 or greater, 1.48 or greater, 1.49 orgreater, or 1.50 or greater. The SMP IOL's and SMP materials may have arefractive index of at least 1.45, at least 1.46, at least 1.47, atleast 1.48, at least 1.49, or at least 1.50.

The SMP IOL's and SMP materials may have an equilibrium water content of8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less,2% or less, 1% or less, or 0.5% or less. The SMPs may have anequilibrium water content (EWC) of 0.5-3.0%. EWC may be gravimetricallydetermined by comparison of dry and hydrated sample weight. For example,first, the dry sample weight is obtained, then the sample is placed in asuitable container and equilibrated in de-ionized H₂O at a prescribedtemperature and time period (e.g., at least 24 h). The sample may thenbe removed from the de-ionized H₂O, excess surface water removed and thesample weighed. EWC may be determined by the following formula: %EWC=[(wt_(hyd)−wt_(dry))/wt_(hyd)]×100.

The SMP IOLs and SMP materials disclosed herein may exhibit little or noglistening. The term “glistenings,” may refer to small, light reflectiveregions in an IOL structure. It is believed that glistenings may becaused by water entry into vacuoles in a polymeric matrix of an IOL,changing the refractive index of the lens at those points, which changeappears as reflective spots or “glistenings.” Glistenings can causeglare and other annoyances to patients who have implanted IOLs.Glistening may be measured by placing a sample (e.g., a coupon, lens,disk) in distilled water maintained at a selected temperature (e.g., 50°C.) for a selected time period (e.g., 72 hours). The sample maythereafter be removed from the DI water and inspected under a stereomicroscope and/or by slit lamp microscopy. Magnifications of 10-80× maybe used. The entire sample may be analyzed on both sides as well as atvarious angles to ensure complete inspection of the sample. A sample maybe judged to have no glistenings if the number of glistenings detectedin the eyepiece is zero.

Monomers for Manufacture of SMP Materials

SMP materials may be prepared from one or more monomers. The SMPcomponents and amounts thereof may be selected in order to attenuateand/or select for various properties, such as shape memory, glasstransition temperature, UV-blocking, refractive index, equilibrium watercontent (EWC), and glistening.

In certain embodiments, the SMP polymer segments can be natural orsynthetic, although synthetic polymers are preferred. The polymersegments may be nonbiodegradable. Non-biodegradable polymers used formedical applications preferably do not include aromatic groups, otherthan those present in naturally occurring amino acids. The SMP utilizedin the IOLs disclosed herein may be nonbiodegradable. In someimplementations, it may be desirable to use biodegradable polymers inthe SMP IOLs, for example, when temporary sterilization is desired oradditional functionality is necessary.

The polymers may be selected based on the desired glass transitiontemperature(s) (if at least one segment is amorphous) or the meltingpoint(s) (if at least one segment is crystalline), which in turn isbased on the desired application, taking into consideration theenvironment of use. Representative natural polymer blocks or polymersinclude proteins such as zein, modified zein, casein, gelatin, gluten,serum albumin, and collagen, and polysaccharides such as alginate,celluloses, dextrans, pullulane, and polyhyaluronic acid, as well aschitin, poly(3-hydroxyalkanoate), especially poly(3-hydroxybutyrate),poly(3-hydroxyoctanoate), and poly(3-hydroxyfatty acids). Representativenatural biodegradable polymer blocks or polymers include polysaccharidessuch as alginate, dextran, cellulose, collagen, and chemical derivativesthereof (substitutions, additions of chemical groups, for example,alkyl, alkylene, hydroxylations, oxidations, and other modificationsroutinely made by those skilled in the art), and proteins such asalbumin, zein, and copolymers and blends thereof, alone or incombination with synthetic polymers.

Representative synthetic polymer blocks or polymers includepolyphosphazenes, polyvinyl alcohols), polyamides, polyester amides,poly(amino acid)s, synthetic poly(amino acids), polyanhydrides,polycarbonates, polyacrylates, polyalkylenes, polyacrylamides,polyalkylene glycols, polyalkylene oxides, polyalkylene terephthalates,polyortho esters, polyvinyl ethers, polyvinyl esters, polyvinyl halides,polyvinyl pyrrolidone, polyesters, polylactides, polyglycolides,polysiloxanes, polyurethanes and copolymers thereof. Examples ofsuitable polyacrylates include poly(methyl methacrylate), poly(ethylmethacrylate), poly(butyl methacrylate), poly(isobutyl methacrylate),poly(ethylene glycol dimethacrylate) (PEGDMA), diethylene glycoldimethacrylate (DEGDMA), poly(ethylene glycol) diacrylate (PEGDA),poly(hexyl methacrylate), poly(isodecyl methacrylate), poly(laurylmethacrylate), poly(phenyl methacrylate), poly(ethyl acrylate),poly(methyl acrylate), poly(isopropyl acrylate), butyl acrylate,poly(butyl acrylate), poly(tert-butyl acrylate), poly(isobutylacrylate), poly(isobornyl acrylate) and poly(octadecyl acrylate).

Synthetically modified natural polymers include cellulose derivativessuch as alkyl celluloses, hydroxyalkyl celluloses, cellulose ethers,cellulose esters, nitrocelluloses, and chitosan. Examples of suitablecellulose derivatives include methyl cellulose, ethyl cellulose,hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxybutylmethyl cellulose, cellulose acetate, cellulose propionate, celluloseacetate butyrate, cellulose acetate phthalate, carboxymethyl cellulose,cellulose triacetate, and cellulose sulfate sodium salt. These arecollectively referred to herein as “celluloses.”

Representative synthetic degradable polymer segments include polyhydroxyacids, such as polylactides, polyglycolides and copolymers thereof;poly(ethylene terephthalate); polyanhydrides, poly(hydroxybutyric acid);poly(hydroxyvaleric acid); poly[lactide-co-(s-caprolactone)];poly[glycolide-co-(s-caprolactone)]; polycarbonates, poly(pseudo aminoacids); poly(amino acids); poly(hydroxyalkanoate)s; polyanhydrides;polyortho esters; and blends and copolymers thereof. Polymers containinglabile bonds, such as polyanhydrides and polyesters, are well known fortheir hydrolytic reactivity. The hydrolytic degradation rates of thesepolymer segments can generally be altered by simple changes in thepolymer backbone and their sequence structure.

Examples of non-biodegradable synthetic polymer segments includeethylene vinyl acetate, poly(meth)acrylic acid, polyamides,polyethylene, polypropylene, polystyrene, polyvinyl chloride,polyvinylphenol, and copolymers and mixtures thereof. The polymers canbe obtained from commercial sources such as Sigma Chemical Co., St.Louis, Mo.; Polysciences, Warrenton, Pa.; Aldrich Chemical Co.,Milwaukee, Wis.; Fluka, Ronkonkoma, N.Y.; and BioRad, Richmond, Calif.Alternatively, the polymers can be synthesized from monomers obtainedfrom commercial sources, using standard techniques.

In some implementations, thiol-vinyl and thiol-yne polymer compounds asdisclosed in international application no. PCT/US2009/041359 entitled“Thiol-vinyl and thiol-yne systems for shape memory polymers” filed 22Apr. 2009, which is hereby incorporated by reference herein in itsentirety, may be used to form IOLs. In other implementations, polymerformulations may undergo a two-stage curing process in which a second,photo-induced polymerization of still unreacted functional groups isundertaken after an initial cure stage. Such a dual cure system formanufacturing SMP materials is described in U.S. provisional patentapplication No. 61/410,192 entitled “Dual-cure polymer systems” filed 10Nov. 2010, which is hereby incorporated by reference herein in itsentirety.

In certain embodiments, tert-butyl acrylate (tBA) can be used to impartshape memory properties to SMP materials. Such monomer may be providedin an amount of 50 wt % to 85 wt %, or 60 wt % to 75 wt %, based ontotal weight of the SMP formulation. Such monomer may be provided in anamount of about 50 wt %, about 55 wt %, about 60 wt %, about 65 wt %,about 70 wt %, about 75 wt %, about 80 wt %, or about 85 wt %, based ontotal weight of the SMP formulation.

In certain embodiments, n-butyl acrylate (nBA) can be used to modify theglass transition temperature of SMP materials. Such monomer may beprovided in an amount of 0 wt % to 20 wt %, 0 wt % to 15 wt %, or 0 wt %to 10 wt %, based on total weight of the SMP formulation. Such monomermay be provided in an amount of about 0 wt %, about 5 wt %, about 10 wt%, about 15 wt %, or about 20 wt %, based on total weight of the SMPformulation.

In certain embodiments, 2-hydroxy-3-phenoxypropyl acrylate (HPPA) can beused to increase the refractive index of SMP materials. Such monomer maybe provided in an amount of 0 wt % to 20 wt %, 0 wt % to 15 wt %, 0 wt %to 10 wt %, 15 wt % to 20 wt %, or 16 wt % to 18 wt %, based on totalweight of the SMP formulation. Such monomer may be provided in an amountof about 0 wt %, about 5 wt %, about 10 wt %, about 15 wt %, or about 20wt %, based on total weight of the SMP formulation.

Monomers suitable as cross-linkers to prepare SMP materials include, butare not limited to, poly(ethylene glycol) dimethacrylate polymer(PEGDMA), and diethylene glycol. In certain embodiments, thecross-linker is a PEGDMA polymer. The PEGDMA may have a number averagemolecular weight (M_(n)) ranging from 500 g/mol to 2,000 g/mol. Incertain embodiments, the cross-linker is selected from the groupconsisting of PEGDMA 550, PEGDMA 750, PEGDMA 1000, and PEGDMA 2000, orany combination thereof. In certain embodiments, the cross-linker isPEGDMA 750. In certain embodiments, the cross-linker is PEGDMA 1000.

In certain embodiments, the cross-linker is diethylene glycol.

The cross-linker may be provided in an amount of 3 wt % to 25 wt %, 5 wt% to 20 wt %, or 8 wt % to 12 wt %, based on total weight of the SMPformulation. Such monomers may be provided in an amount of about 5 wt %,about 10 wt %, about 15 wt %, about 20 wt %, or about 25 wt %, based ontotal weight of the SMP formulation.

Monomers suitable as UV-blockers for inclusion in SMP materials include,but are not limited to, benzophenones and benzotriazoles. In certainembodiments, the UV-blocker is selected from the group consisting of amethacryloyl chlorobenzotriazole, a methacryloyl methoxybenzotriazole,and a yellow dye, or any combination thereof. Suitable methacryloylchlorobenzotriazoles include 2-methylacrylic acid3-[3-tert-butyl-5-(5-chlorobenzotriazol-2-yl)-4-hydroxyphenyl]-propylester (UVB), and2-(2-hydroxy-3-tert-butyl-5-vinylphenyl)-5-chloro-2H-benzotriazole(UVAM). A suitable methacryloyl methoxybenzotriazole is3-(tert-butyl)-4-hydroxy-5-(5-methoxy-2H-benzo[d][1,2,3]triazol-2-yl)phenethylmethacrylate. A suitable yellow dye is(E)-2-(2-cyano-3-(4-(1,1-dioxidothiomorpholino)phenyl)acrylamido)ethylmethacrylate).

Preferred UV blockers include the benzotriazole class of compounds.Benzotriazoles are generally more efficient at blocking UV than arebenzophenones. In certain embodiments, chlorobenzotriazoles arepreferred, and in particular, chlorobenzotriazoles polymerizable by freeradical mechanisms. In certain embodiments, methoxybenzotriazoles arepreferred, and in particular, methoxybenzotriazoles polymerizable byfree radical mechanisms. Particularly preferred UV blockers includemethacrylate-functional chloro-substituted benzotriazoles andmethacrylate-functional methoxy-substituted benzotriazoles.

Chlorobenzotriazoles and methoxybenzotriazoles exhibit a maximumabsorbance at higher wavelengths than standard benzotriazoles. Thechloro-substitution and methoxy-substitution shift the peak absorptionof the molecule toward the visible range (e.g., closer to 400 nm). Thehigher UV-blocking efficiency, combined with the shift of the peakabsorbance wavelength, may allow incorporation of such UV benzotriazoleblockers at lower concentrations compared to benzophenones, whileproducing effective filtration of the entire UV spectrum (e.g., up to400 nm).

In certain embodiments, a combination of benzotriazole UV-blockers maybe used. For example, a standard benzotriazole UV-blocker may be used toblock a lower wavelength portion of the UV spectrum (having a lower peakabsorbence) and a chloro-substituted and/or methoxy-substitutedbenzotriazole may be used to block a higher wavelength portion of the UVspectrum (e.g., closer to 400 nm).

The methacrylate functionality of the UV-blockers may be beneficial tothe SMP formulation compared to vinyl-allyl- or other functionality, asthe methacrylate functionality may provide suitable reaction kineticsfor monomer incorporation into a shape memory polymer, particularlywhere the other monomers (e.g., cross-linkers) include methacrylatefunctionalities as the polymerizable functional group.

In certain embodiments, yellow dyes are beneficial to the formulation asa means to filter the violet range of the visible light spectrum.Methoxybenzotriazoles may be an alternative to yellow dyes.

Suitable UV-blockers are shown in Table 1.

TABLE 1 UV Blocker Structure CAS # Methacryloyl Chlorobenzotriazole

96478-15-8 UVAM

124883-10-9 Yellow Dye

N/A Methacryloyl Methoxybenzotriazole

N/A

The UV-blocker may be provided in an amount of 0.2 wt % to 2 wt %, 0.25wt % to 1.5 wt %, or 0.5 wt % to 1 wt %, based on total weight of theSMP formulation. Such monomers may be provided in an amount of about 0.2wt %, about 0.3 wt %, about 0.4 wt %, about 0.5 wt %, about 0.6 wt %,about 0.7 wt %, about 0.8 wt %, about 0.9 wt %, about 1.0 wt %, about1.1 wt %, about 1.2 wt %, about 1.3 wt %, about 1.4 wt %, or about 1.5wt %, based on total weight of the SMP formulation.

Manufacturing of SMP IOLs may be achieved through either thermalinitiation, photo-initiation, or a combination of the two processes.Monomers suitable as polymerization initiators include, but are notlimited to, 2,2-dimethoxy-2-phenylacetophenone (Irgacure 651),phenylbis(2,4,6-trimethylbenzoyl) phosphine oxide (Irgacure 819),azobisisobutyronitrile (AIBN), lauroyl peroxide,di(4-tert-butylcyclohexyl) peroxydicarbonate (Perkadox 16),camphorquinone, and diphenyl-(2,4,6-trimethylbenzoyl)-phosphine oxide(TPO). In certain embodiments, the polymerization initiator is lauroylperoxide. Thermal and photo initiators that may be used for theformulations are listed in Table 2.

TABLE 2 Initiator Structure CAS # Lauroyl Peroxide

105-74-8 2,2′-Azobis(2- methylpropionitrile) (AIBN)

78-67-1 Di(4-tert- butylcyclohexyl) peroxydicarbonate (Perkadox 16)

15520-11-3 Phenylbis(2,4,6- trimethylbenzoyl) phosphine oxide (Irgacure819)

162881-26-7 2,2-Dimethoxy-2- phenylacetophenone (Irgacure 651)

24650-42-8 Camphorquinone

10373-78-1 Diphenyl-(2,4,6- trimethylbenzoyl)- phosphine oxide (TPO)

75980-60-8

In certain embodiments, the shape memory polymer formulation may bepolymerized using a photoinitiator. For example, the shape memorypolymer formulation may be polymerized using Irgacure 651 as aphotoinitiator, preferably when UV-blockers are absent in theformulation. The shape memory polymer formulation may be polymerizedusing Irgacure 819 as a photoinitiator, preferably when UV-blockers arepresent in the formulation. Irgacure 819 is capable of absorbing lightinto the visible range, allowing it to remain effective as aphotoinitiator when mixed with competing UV absorbing components.

In certain embodiments, the shape memory polymer formulation may bepolymerized using a thermal initiator. For thermal initiation, bothperoxides and azo initiators may be utilized. Suitable thermalinitiators include, but are not limited to, AIBN, lauroyl peroxide, andPerkadox 16. Thermal initiators may be preferred when fabricating IOLsvia cryolathing.

In certain embodiments, a dual initiation system (photo and thermalcuring) may be used to affect polymerization of the shape memory polymerformulation. The formulation may be initially cured by photoinitiationin order to quickly gel the polymer. The polymerization reaction may bedriven to completion (high monomer-to-polymer conversion) by eithercontinued photoinitiation or by thermal initiation. The thermalinitiation may be driven as a separate process in which the polymer istransferred to a hot oven or bath.

In certain embodiments, the addition of a mix of photo and thermalinitiators may drive a simultaneous mechanism. For example, irradiationof a monomer formulation with light (UV or visible) may initiatepolymerization by photochemical reaction. The exothermic nature of thefree radical polymerization may induce further polymerization via athermal mechanism. A more reactive thermal initiator such as Perkadox 16may be preferred for such a dual initiation system.

The initiator may be provided in an amount of 0.01 wt % to 5 wt %, 0.05wt % to 3 wt %, 0.05 wt % to 1 wt %, 0.1 wt % to 0.5 wt %, or 0.1 wt %to 0.2 wt %, based on total weight of the SMP formulation. The initiatormay be provided in an amount of about 0.01 wt %, about 0.05 wt %, about0.10 wt %, about 0.15 wt %, about 0.20 wt %, about 0.25 wt %, about 0.30wt %, about 0.35 wt %, about 0.40 wt %, about 0.45 wt %, about 0.5 wt %,about 1 wt %, about 2 wt %, or about 3 wt %, based on total weight ofthe SMP formulation. Formulations vary in quantity of initiator tooptimize cycle time during the manufacturing process and still maintaindesired thermomechanical properties.

In certain embodiments, a colorant may be added to the SMP formulations.SMP materials with SPECTRAFLO (trademark of Ferro) liquid may beprepared. The formulations may include 0.1 wt % to 2 wt % colorant,based on total weight of the SMP formulation. Various colors may beadded while maintaining desired thermomechanical properties.

In certain embodiments, a SMP material or network may include dissolvingmaterials which may include part of the network or may be included inthe formulation of the network before the network is polymerized (e.g.,as an aggregate, mixed into the formulation). Dissolving materials mayinclude materials that disperse over time, even if the material or partof the material does not actually dissolve or enter into a solution witha solvent. In other words, a dissolving material as used herein may beany material that may be broken down by an anticipated externalenvironment of the polymer. In one embodiment, a dissolving material isa drug which elutes out of a SMP network. A dissolving material may beattached by chemical or physical bonds to the polymer network and maybecome disassociated with the polymer network over time.

Dissolving materials, through their dissolution over time, may be usedfor many purposes. For example, the dissolution of a material may affecta dissolution or break-up of a biomedical device over time.Alternatively, the dissolution of a material may elute a drug, achievinga pharmacological purpose. Medications or drugs can be infused into SMPdevices to aid in healing (e.g., anti-inflammatory), avoid complications(e.g., anti-thrombotic), or to combat potential infection (e.g.,antibiotic). Medications may be added by injection into the liquidpolymer before curing. Medications may also be added to SMP devicespost-polymerization using various surface modification or coatingtechniques, for example, plasma deposition.

Exemplary SMP Formulations

Some exemplary SMP formulations and their measured properties arereported in Table 3 below. In one formulation, tert-butyl acrylate (tBA)is combined with poly(ethylene glycol) dimethacrylate (PEGDMA) 1000 as across-linker. The weight percentages of each may be varied to design anSMP with particular desired material properties.

TABLE 3 Max Compres- Rubbery Tensile sive Tg Modulus Strain StrainGlistening Formulation (° C.) (MPa) RI (%) (%) Properties tBa (78%); 402.5 1.465 >250 >65 Glistening PEGDMA Free 1000 (22%) tBA (65%); 25 2.51.475 >125 >65 Glistening nBA (13%); Free PEGDMA 1000 (22%) tBA (50%);17 2.5 1.468 >100 >65 Glistening isobutyl Free acrylate (28%); PEGDMA1000 (22%)

As one example of the optimization, recovery time is controlled by therelationship of the glass transition temperature (Tg) of the SMPmaterial used to the environmental temperature (Te) in which an SMPdevice is deployed. A Tg<Te deploys more slowly than a Tg=Te, and aTg>Te deploys at the fastest rate. Tg of the material may be controlledfrom −35° C. up to 114° C., allowing a wide range of control over thedeployment rate into the body. Desirable ranges for Tg in IOL devicesmay be between 10° C. and 60° C., and even more desirably between 15° C.and 45° C. Devices have been created that deploy in less than a secondall the way up to several minutes to fully deploy.

The ability to change refractive index has also been investigatedthrough changes to the SMP formulation. Table 4 below provides data onthe refractive index of the different components used in severalexemplary formulations.

TABLE 4 Refractive Index @ Function- Chemical Name 36° C. alitytert-Butyl Acrylate (tBA) 1.4031 Monomer Poly(ethylene glycol)dimethylacrylate 1.4609 Cross-linker (PEGDMA) 550 Poly(ethylene glycol)dimethylacrylate 1.460 Cross-linker (PEGDMA) 1000 Polycarbonate (PC)Diacrylate 610 1.4635 Cross-linker KIFDA 542 (King Industries, Inc.,1.475 Cross-linker Norwalk, CT) Bisphenol A propoxylate diacrylate 1.515Cross-linker (BPA-P) Diacrylate Poly(ethylene glycol) diacrylate 1.467Cross-linker (PEGDA) 575 Poly(ethylene glycol) diacrylate 1.47Cross-linker (PEGDA) 700

While certain molecular weights of the cross-linkers are presented withmeasured refractive indexes in Table 4, other molecular weights can beuses in varying formulations. For example, poly(ethylene glycol)diacrylate (PEGDA), poly(ethylene glycol) diacrylate (PEGDA) may be usedwith good result in various molecular weights of between 500 and 2000.

SMP samples listed in Table 5 below were created and the refractiveindices were measured. Cross-linking of 20% for the noted cross-linkerpolymer was used. The results show only slight changes to the refractiveindex values based on the formulations created. Increasing the contentof the cross-linker in the formulations may be used to change therefractive index values more. In addition, other formulations may beprepared with poly(carbonate) diacrylate, KIFDA-542 diacrylate(available from King Industries, Inc., Norwalk, Conn.), and bisphenol-Apropoxylate diacrylate that have a greater effect on changing therefractive index.

TABLE 5 Tg Glistening Formulation (° C.) RI Evaluation tBA (80%):PEGDMA550 (20%) 52 1.465 glistens tBA (64%):nBA (24%):PEGDMA 32 glistens 550(12%) tBA (78%):PEGDMA 1000 (22%) 40 1.465 does not glisten tBA(60%):nBA (20%):PEGDMA 30 glistens 550 (20%) tBA (56%):nBA (14%):PEGDMA32 glistens 550 (30%) tBA (80%):PC-DA (20%) 59 1.463 glistens tBA(78%):SR601 (22%) 71 1.48 does not glisten tBA (78%):SR602 (22%) 521.478 does not glisten tBA(78%):CD9038(22%) 41 1.468 does not glistentBA (65%):nBA 25 1.475 does not glisten (13%):PEGDMA 1000 (22%) tBA(78%):PEGDMA 1000 40 1.465 does not glisten (22%):BTA (.5%) tBA(78%):PEGDMA 1000 40 1.465 does not glisten (22%):BTA (1%) isobutylA(78%):PEGDMA −13.5 1000 (22%) nBA (78%):PEGDMA 1000 (22%) −27.5 tBA(50%):isobutylA 17.5 1.468 does not glisten (28%):PEGDMA 1000 (22%) HPPA(78%):PEGDMA 1000 (22%) 23 1.542 does not glisten HPMAEP (78%):PEGDMA1000 (22%) 34 1.536 does not glisten tBA (60%):PEGDMA 1000 (40%) 18 doesnot glisten tBA (76%):isobutylA 43 (14%):PEGDMA 1000 (10%) tBA(85%):PEGDMA 1000 (15%) 48

The ability to change light transmission properties through the SMPmaterials has been investigated.2-[3-(2H-Benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate (BTA) wasadded to the SMP IOL formulation as an ultraviolet (UV) wavelengthblocker, as indicated in the table above. Two formulations with 0.5% UVblocker and 1% UV blocker were created and then analyzed for UV throughvisible wavelength transmission and dynamic mechanical analysis. FIG. 1is a graph showing the storage modulus and the tan delta (the ratio ofthe storage modulus to the loss modulus) of the following three materialformulations over a range of temperatures from 0 to 100° C.:

SMP106: 78% tBA and 22% PEGDMA 1000 with no UV blocker;

SMP122: SMP106 with 0.5 weight % BTA functionalized UV blocker added;and

SMP123: SMP106 with 1.0 weight % BTA functionalized UV blocker added.

The upper curve is the storage modulus and the lower curve is the tandelta. As is apparent, the addition of the small amounts of BTA as a UVblocker has little if any effect on the modulus of the SMP materials andthe Tg (the peak of the tan delta curve) is constant for all threeformulations.

FIG. 2 shows the effect of the addition of the BTA UV blocker on the SMPmaterials of FIG. 1. As is apparent, the addition of the UV blocker hasnegligible effect on light transmission in the visible wavelengths, butsharply attenuates wavelengths below about 380 nm, which is the upperend of the UV spectrum.

FIG. 3 is a graph showing the storage modulus and the tan delta of twoadditional SMP formulations over a range of temperatures from −20 to100° C. in comparison to SMP 106:

SMP119: 65 wt % tBA, 13 wt % butyl acrylate, 22 wt % PEGDMA 1000; and

SMP126: 50 wt % tBA, 28 wt % isobutyl acrylate, 22 wt % PEGDMA 1000.

The upper curve is the storage modulus and the lower curve is the tandelta. The difference in formulas provides different Tg for use indifferent environments and for different applications in which it may beuseful to have a lower transition temperature. SMP119 has a Tg of about25° C. and SMP126 has a Tg of about 17° C. However, even with thedifferences in Tg, the storage moduli of the SMP 119 and SMP126formulations compare favorably to the SMP106 material. FIG. 4 alsoindicates that the light transmission properties of SMP119 and SMP126compare favorably to the SMP106 formula.

FIG. 5 is a graph depicting stress-strain data curves for SMP106,SMP119, and SMP126 for the materials under compression. As is apparent,the SMP119 and SMP126 formulas exhibit significantly less stress under acompressive strain of 65% compared to the SMP106 formula. This allowsthese materials to be more easily deformed at lower temperatures, suchas room temperature. FIG. 6 is another stress-strain curve for SMP106for two separate rates of elongation under tension, i.e., for rates of10 mm/min and 20 mm/min. As shown in the graph, SMP106 performs quitewell under tension and withstood up to and over 250% strain at bothrates.

SMP106 was used as the basis for the development of additionalformulations including UV-blockers. Initially, 2-methylacrylic acid3-[3-tert-butyl-5-(5-chlorobenzotriazol-2-yl)-4-hydroxyphenyl]-propylester (UVB) and2-(2-hydroxy-3-tert-butyl-5-vinylphenyl)-5-chloro-2H-benzotriazole(UVAM) were each incorporated into the SMP106 formulation at 0.5 wt %,1.0 wt % and 2.0 wt % to determine the amount needed to achieve 10%transmission (T) cut-off at 400 nm. UV/Vis transmission was run onsamples containing each of these blockers. Due to the addition of the UVblockers and the absorption spectrum of DMPA, the initiator was switchedto a compound that absorbs in the visible spectrum.Bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide (IRGACURE 819) waschosen due to its absorption characteristics in the visible range above400 nm. The results are shown in Table 6.

TABLE 6 % Transmission Formulation at 400 nm SMP208: 14.20tBA(77.5%):UVB(0.5%):PEGDMA1000(22%):IRGACURE819(0.15%) SMP209: 2.39tBA(77.0%):UVB(1.0%):PEGDMA1000(22%):IRGACURE819(0.15%) SMP210: 0.37tBA(76.0%):UVB(2.0%):PEGDMA1000(22%):IRGACURE819(0.15%) SMP211: 10.39tBA(77.5%):UVAM(0.5%):PEGDMA1000(22%):IRGACURE819(0.15%) SMP212: 1.59tBA(77.0%):UVAM(1.0%):PEGDMA1000(22%):IRGACURE819(0.15%) SMP213: 0.03tBA(76.0%):UVAM(2.0%):PEGDMA1000(22%):IRGACURE819(0.15%)

Based on the results from this initial data, a linear fit was used todetermine the amount of each UV blocker needed to achieve the 10% Tcut-off at 400 nm. This was determined to be 0.7 wt % of the UVB blockerand 0.55 wt % of the UVAM blocker. The following high Tg and low Tgformulations were created with these blocker amounts, as shown in Table7.

TABLE 7 % Transmission Tg Formulation at 400 nm (° C.) SMP214: 6.37 41tBA(77.3%):UVB(0.7%):PEGDMA1000(22%):IRGACURE819(0.15%) SMP215: 9.30 41tBA(77.45%):UVAM(0.55%):PEGDMA1000(22%):IRGACURE819(0.15%) SMP218: 6.2825 tBA(64.30%):nBA(13.0%):UVB(0.7%):PEGDMA1000(22%):IRGACURE819(0.15%)SMP219: 7.79 25tBA(64.45%):nBA(13.0%):UVAM(0.55%):PEGDMA1000(22%):IRGACURE819(0.15%)

Polymerization Parameters and Coupon Preparation for Formulations 214,215, 218, and 219

Liquid monomer solutions of the 214, 215, 218 and 219 formulations werecreated by mixing the individual monomer components. A 20 mlscintillation vial was placed on a balance with 0.1 mg resolution. Theindividual monomer components were added to the vial in the specifiedamounts. Lastly the initiator was added and the vials were wrapped infoil to protect the mixture from light. The monomer solutions were mixedon a heated stir plate at 45° C. and 500 rpm for 20 minutes. Eachformulation was then visually inspected to ensure complete mixing of thecomponents. The formulations were stored protected from light until usedfor polymerization.

Light polymerization was used to cure all polymer samples. The liquidmonomer solutions were injected in between two glass microscope slidesspaced 1 mm apart. The glass slides were treated with glassclad 18. Theslides were exposed to 320-500 nm collimated light at 40 mW/cm² for 10mins, flipped and the bottom side was exposed for an additional 10minutes. Upon completion of photo-curing the polymer samples were set inan oven at 90° C. for 1 hour. Upon completion of the heat treatment, thepolymer slides were removed from the molds and allowed to cool.

Two polymer slides of each formulation were produced. The slides werethen cut as shown in FIG. 15. In order to meet the requirements for therefractive index measurements, larger samples 20 mm×8 mm×3 mm werecreated specifically for this test using the same polymerizationconditions.

Transmission Tests for Formulations 214, 215, 218, and 219

Polymer coupons 1 mm thick of each formulation 214, 215, 218 and 219were placed in a custom sample holder and inserted into a quartzcuvette. The cuvette was filled with distilled water and placed in theUV-Vis spectrophotometer. Four coupons of each formulation from twodifferent slides were measured in transmission mode. The samples werescanned from 190 nm-1100 nm at 1 nm resolution. The transmission datafor all four systems is given in Table 8. One transmission curve foreach formulation is shown in FIG. 16.

TABLE 8 Wave- length Average Transmission (n = 4) (nm) SMP214 SMP215SMP218 SMP219 300  0.00 ± 0.01  0.00 ± 0.01  0.02 ± 0.00  0.00 ± 0.01365  0.01 ± 0.01  0.02 ± 0.03  0.03 ± 0.02  0.00 ± 0.02 400  6.37 ± 0.28 9.30 ± 0.31  6.28 ± 0.16  7.79 ± 0.38 440 97.53 ± 0.19 97.24 ± 0.3294.43 ± 1.54 93.75 ± 1.12 600 98.96 ± 0.16 98.80 ± 0.35 95.85 ± 1.4995.72 ± 0.94 800 99.13 ± 0.24 99.00 ± 0.25 96.51 ± 1.40 96.54 ± 0.69

Refractive Index and EWC of Formulations 214, 215, 218, 219, and 230b

Formulations 214, 215, 218 and 219 exhibited great incorporation of theUV blocker, however the low refractive index (RI) and high equilibriumwater content (EWC) of these materials necessitated additionalformulations. Table 9 provides an overview of the RI and EWC values forthese formulations and an additional formulation, SMP230. In order toincrease the RI, 2-hydroxy-3-phenoxypropyl acrylate (HPPA) wasincorporated into the system. Additionally, the hydrophilic PEGDMA1000content was scaled back in an effort to decrease the EWC. The UVBblocker was chosen due to its increased reactivity from the methacrylatefunctionality compared to the UVAM monomer. Table 10 outlines theSMP230b formulation.

TABLE 9 RI EWC Formulation (Hydrated at 35° C.) (%) at 35° C. SMP2141.4597 7.82 SMP215 1.4574 7.78 SMP218 1.4589 7.75 SMP219 1.4584 8.08SMP230 1.4709 1.66

TABLE 10 ID Formulation SMP230btBA(59.80%):nBA(12.00%):HPPA(17.50%):UVB(0.70%):PEGDMA1000(10%):LP(0.15%)

Polymerization Parameters and Coupon Preparation for Formulations 230b

Liquid monomer solutions of the SMP230b formulation were created bymixing the individual monomer components. A 20 ml scintillation vial wasplaced on a balance with 0.1 mg resolution. The individual monomercomponents were added to the vial in the specified amounts. Lastly theinitiator was added and the vials were wrapped in foil to protect themixture from light. Each formulation was then visually inspected toensure complete mixing of the components. The formulations were storedprotected from light and heat until used for polymerization.

Thermal polymerization using Lauroyl Peroxide (LP) was used to cure thepolymer samples. The liquid monomer solutions were injected between twoglass microscope slides spaced either 0.7 mm or 1.4 mm apart. Viton wasused for the gasket due to its working temperature range. Theformulations were cured in the mold in a water bath at 80° C. for 2hours and then transferred to an oven to cure for an additional 2 hoursat 90° C. The degree of polymerization was monitored at specifiedintervals using FTIR to measure double bond conversion. Upon completionof the polymerization, the polymer samples were removed from the moldsand allowed to cool.

Transmission Tests for Formulation 230b

Polymer coupons 0.7 mm thick and 1.4 mm thick of the SMP230b formulationwere placed in a custom sample holder and inserted into a quartzcuvette. The cuvette was filled with distilled water and placed in theUV-Vis spectrophotometer. Three coupons were measured in transmissionmode. The samples were scanned from 190-1100 nm at 1 nm resolution. Thetransmission data for the samples are given in Table 11 (lighttransmittance of Sample A (sa) at 0.7 mm thick) and Table 12 (lighttransmittance of Sample B (sb) at 1.4 mm thick). One transmission curvefor each thickness is shown in FIG. 17.

TABLE 11 Wave- SMP230b- SMP230b- SMP230b- length sa_01 sa_02 sa_03Average Std Dev 800 98.78 97.66 98.83 98.43 0.66 600 98.39 97.60 98.0298.01 0.40 440 97.71 96.53 96.58 96.94 0.67 400 12.46 11.92 12.13 12.170.27 365 −0.01 0.02 0.02 0.01 0.02 300 0.00 0.01 0.01 0.01 0.01

TABLE 12 Wave- SMP230b- SMP230b- SMP230b- length sb_01 sb_02 Sb_03Average Std Dev 800 98.02 95.88 97.90 97.27 1.21 600 97.44 94.91 97.2596.54 1.41 440 94.81 92.87 95.47 94.39 1.35 400 1.17 1.02 1.27 1.16 0.13365 0.02 0.02 0.01 0.02 0.01 300 0.01 0.01 0.00 0.01 0.00

Refractive Index and EWC of SMP230 Formulations

An Abbe refractometer was used to make RI measurements for formulation230. Polymer coupons of each formulation were polymerized as describedabove and 6 mm diameter buttons were cut for the testing. The polymersample was placed on the refractometer prism and allowed to acclimate totemperature for 1 minute. The RI value was measured and recorded. The RIdata is presented in Table 13. The samples were then hydrated in DIwater at 350 and the measurements were performed again. EWC data arepresented in Table 14.

TABLE 13 RI, Dry 25° C. RI, Dry 35° C. RI, Hydrated 35° C. Sample Rep 1Rep 2 Avg Rep 1 Rep 2 Avg Rep 1 Rep 2 Avg 230-1 1.4748 1.4759 1.47541.4722 1.4718 1.4720 1.4702 1.4710 1.4706 230-2 1.4752 1.4755 1.47541.4720 1.4721 1.4721 1.4702 1.4712 1.4707 230-3 1.4750 1.4745 1.47481.4718 1.4715 1.4717 1.4710 1.4708 1.4709 Average Std Dev Average StdDev Average Std Dev 1.4752 0.0005 1.4719 0.0002 1.4709 0.0002

TABLE 14 Weights % H₂O Sample Dry 3 days 5 days 3 days 5 days 230b-10.0236 0.0240 0.0240 1.67% 1.67% 230b-2 0.0240 0.0244 0.0244 1.64% 1.64%230b-3 0.0236 0.0240 0.0240 1.67% 1.67% Average 1.66% 1.66% Std. 0.02%0.02% Dev.

Weight Loss by Exhaustive Extraction of Formulations 214, 215, 218, 219,and 230b

Polymer coupons were run through and an in process extraction under thefollowing parameters. The samples were vacuum dried at 60° C. and −40torr for 72 hours. The mass of six coupons for formulations 214, 215,218, and 219 were measured, and the mass of ten coupons from twodifferent polymer batches for 230b were measured. The coupons wereplaced in Acetonitrile and maintained at 35° C. for 72 hours. Couponswere then removed from the Acetonitrile and allowed to air dry for 8hours. Following the air dry the samples were dried in a vacuum oven for72 hours. Following the in process extraction an exhaustive extractionin acetonitrile was performed. The mass loss results of the exhaustiveextraction are reported in Table 15.

TABLE 15 Formulation Average Mass Loss (n = 6) SMP214 0.73% ± 0.11SMP215 0.73% ± 0.14 SMP218 0.83% ± 0.06 SMP219 0.81% ± 0.09 Average MassLoss (n = 10) SMP230b 0.22% ± 0.06

Glistening of Formulations 214, 215, 218, 219, and 230b

Coupons were placed in distilled water and maintained at a temperatureof 50° C. for 72 hours. The coupons of each formulation were removedfrom the DI water and inspected under a stereo microscope.Magnifications of 10-80× were used. The entire coupon was analyzed onboth sides as well as at various angles to ensure complete inspection ofeach sample. Table 16 shows that formulations 214, 215, 218, 219, and230b exhibited no glistening.

TABLE 16 Glistening Formulation Observation SMP214 no glistening SMP215no glistening SMP218 no glistening SMP219 no glistening SMP230b noglistening

Cytotoxicity of Formulations 214, 215, 218, 219, and 230b

Rectangular samples were extracted in acetonitrile as described above.Samples totaling a mass of 4 g were sent out for cytotoxicity testingwith a specified extraction ration of 4 g/20 ml.

Based on the foregoing, in certain embodiments, exemplary shape memorypolymers as disclosed herein may be derived from tertbutyl acrylate(tBA), one or more PEGDMA monomers (e.g., PEGDMA 1000), one or moreUV-blockers, one or more initiators (photo and/or thermal), optionallyn-butyl acrylate (nBA), and optionally 2-hydroxy-3-phenoxypropylacrylate (HPPA).

Optionally, one formulation may target a glass transition temperature(Tg) near body temperature (34-38° C.); and a second formulation maytarget a lower glass transition temperature (<13° C.). The formulationsmay form a crosslinked high molecular weight polymer via free radicalpolymerization. The mode of polymerization may be photochemical, thermalor a combination of both modes of initiation.

The monomers used for these exemplary formulations are listed in Table17.

TABLE 17 Approximate High Tg Low Tg Range Nominal Nominal Monomer CAS #Purpose (wt %) (wt %) (wt %) tert-Butyl 1663-39-4 Shape Memory 50-85% 71.80% 59.80% Acrylate n-Butyl Acrylate 141-32-2 Modify Tg 0-20% 0.0%12.00% 2-hydroxy-3- 16969-10-1 Increase 0-20% 17.50% 17.50%phenoxypropyl Refractive acrylate Index PEGDMA 25852-47-5 Cross-linker3-25% 10.00% 10.00% UV Blockers Various UV-Blocker 0.25-1.5%    0.70%0.70% Initiator Various Polymerization 0.05-3.0%    0.15% 0.15%Initiator

Higher Tg formulations 235 and 236, as shown in Table 18, were preparedto facilitate the ability to remain compressed at operating roomtemperature and have a controlled deployment upon introduction into theeye.

TABLE 18 ID Formulation SMP235tBA(71.8%):HPPA(17.5%):UVB(0.70%):PEGDMA1000(10%):LauroylPeroxide(0.15%) SMP236tBA(66.8%):HPPA(17.5%):UVB(0.70%):PEGDMA1000(10%):PEGDMA750(5.00%):LauroylPeroxide(0.15%)

Intraocular Leases

SMP intraocluar lenses are designed to be inserted through significantlysmaller incisions than other currently commercially available foldablelens technologies. An exemplary SMP intraocular lens 100 is depicted inFIGS. 1 and 2 and will be discussed in greater detail herein below. Inaddition the lens shape is highly conserved (i.e., there is high shapefixity >98%) after deployment in the eye. An intracapsular bag lens mayhave a shape that creates contact with the anterior capsular leaflet aswell as the capsule just posterior to the equator allowing for adecrease in posterior capsule opacity formation. A ciliary sulcus lensmay have a vault which allows it to avoid trauma to the iris. Ananterior chamber lens may have an appropriate vault to decrease the riskof pupillary block and decrease the risk of trauma to the anteriorchamber angle support structures.

There are many advantages to SMP technology when applied to intraocularlenses. First, the intraocular lens is compressible and deformable. Thisability to compress the material and configure it in a small platformallows for smaller incision sizes for delivery. Such SMP lenses, whichfit through smaller incisions, offer significant benefit. For example,with cataract surgery there is less astigmatism, quicker recovery, andless trauma to the eye with smaller incisions. Also, with lasertechnology and improved ultrasound technology, cataract surgery can beperformed with smaller incisions; the limiting factor with presentoptions is the larger incision size needed for the replacement lens.

A second advantage to the shape memory polymer technology in intraocularlens is that deployment of the lens uses thermomechanical recoveryrather than an elastic recovery process. The formulation can be modifiedto change the time or speed of deployment of the lens. This can varydepending upon the location of needed deployment. For example,deployment near delicate structures, such as in the capsular bag or nearthe corneal endothelium, may require slower, surgeon-tailored deploymentto avoid damage to these structures. This modification of deploymentspeed is not possible with other currently available lens technologies.Also the modulus of the SMP material can be modified to optimize thesoftness of lens material to minimize trauma to eye structures. For eachof the lens types described above, the SMP material properties allow fora slow, tailored deployment, which results in less trauma to the areaswith which the lens optic or haptics come in contact.

A third advantage is the ability to easily modify the refractive indexof the lens. The refractive index can be changed through modificationsof SMP formulation. In addition, the surface curvature of the lens,which is important in designing optical power, can be modified throughthe liquid injection molding process or post molding with cutting suchas with a laser. Further, the curvature of lens as well as therefractive index of the lens can be modified post implantation withheat, UV, or laser light modification.

A fourth advantage is that the surface characteristics and implantationof SMP lenses may decrease inflammation and cellular opacification. Asan example, FIG. 7 is an optical profilometry image of a sample SMP lenssurface showing average surface roughness of 16 nanometers. This lowroughness measure minimizes optical artifacts such as spectral filteringand maximizes optical clarity of the lens. In FIG. 7 the darker areassurrounded by the circles are areas toward the higher end of themeasured roughness on the right-hand scale (i.e., toward the 203 nmmeasurement) while the other dark areas in the image are toward thelower end of measured roughness (i.e., toward the −186 nm measurement).For example, an intracapsular SMP IOL will have contact with thecapsular bag to decrease the movement of the lens, but the smoothness ofthe surface retards the migration of epithelial cells and subsequentformation of posterior capsular opacification.

Since the SMP lens is materially robust, the lenses may be also modifiedwith surface polishing as well as other known mechanisms to reduce theproliferation of cells on the surface of intraocular lenses. In additionthe slow deployment of an SMP lens can minimize cellular opacification.There is a tension between the size of the IOL and the collection ofepithelial cells on the lens due to the tight fit within the capsularbag. For example, an intracapsular lens will have contact with thecapsular bag in a fashion to decrease the migrations of the lens, butthe contact with epithelial cells can lead to subsequent formation ofposterior capsular opacification, especially if the fit is tight and thematerial is unable to pass around the lens. This problem is compoundedif during deployment, the capsular bag is impacted and damaged, whichgenerates increased cell production in response to the trauma.Configurations of standard intraocular lenses to decrease this commoncomplication of cataract surgery and lens placement are well known.However, with SMP lenses, the size and apposition of the implanted SMPlens to the capsular bag can be increased over current lenses because ofthe compressibility and deformability of the SMP lens material and theslow deployment that allows a tight fit while minimizing trauma. Theability to polish the surface further mitigates this problem.

Dual Optic Leases

Larger lenses such as dual optic lenses and other accommodativeintraocular lenses may be used to treat refractive error and presbyopiasimultaneously. Dual optic lenses are generally constructed with aprimary intraocular lens having an optic with a primary optical powerand refractive index, and a secondary intraocular lens having an opticwith a secondary optical power and possibly a different refractiveindex. The secondary optic is typically attached to and spaced apartfrom the primary optic by material struts or similar structures aboutthe periphery of the lenses. The two lenses to act synergistically toallow for both near and distance vision depending on the relationship(e.g., separation distance) between the two optics as well as thegeometric association between the two optics which also may (or may not)be adjustable in each individual patient post implantation.

These dual optic lenses often require larger than conventional incisionsfor entry into the eye. These larger platform lenses may be made withSMP materials, which are highly compressible and deformable allowing forsmaller incisions sizes, and thus can improve surgical outcomes for thereasons stated above. In addition, if formed using SMP materials, theselarger lenses can be deployed more slowly allowing the surgeon toposition the lens in such a fashion as to avoid inadvertent trauma toimportant eye structures and careful apposition to structures in thetarget location. This decreases the trauma risk that these largerplatform lenses could cause in the eye. In addition, these lenses arequite complex and require high precision optics capabilities, which areconserved because of the high shape fixity of the SMP materials.

Other accommodative lenses strive to replicate the functions of thenormal human lens. Mechanisms of accommodation are thought to besecondary to ciliary body contraction and zonular deformation of thelens capsule and a change in lens shape as well as an anterior-posteriormovement of the lens complex. With SMP materials, a lens may be createdwhich has close apposition to the lens capsule in multiple areas so thatthere is an ability to replicate the actions of the native lens. Infact, an SMP lens may be made which expands in the intracapsular space,fills either the whole space or a larger area of the space, and respondsto the ciliary body-zonule actions. In addition, an SMP lens can beinserted through a smaller anterior capsular opening, which may helppreserve the responsiveness of the lens to the native accommodativeprocess. The local dimensions, thickness in particular, of the SMP lensmay be modified post implantation (which may affect local stiffness) ifa change in shape is needed to replicate the accommodation process byadding SMP material into the IOL that is of different cross-link densityand therefore different activation temperature (Tg) and/or differentmodulus.

Phakic Intraocular Leases

A phakic intraocular lens is a lens which is placed in the anteriorchamber through a corneal incision. As with the other intraocular lensesdiscussed above, an SMP phakic lens may be compressed for implantationthrough a much smaller incision than presently available lenses. A SMPphakic lens may also be designed to deploy slowly so there is little tono corneal endothelial or native lens trauma. The tailoredsurgeon-controlled deployment allows for positioning of the hapticsagainst the anterior chamber structures without damaging the trabecularmeshwork or iris. The force placed on the angle structures by thehaptics is consistent and more reproducible than with a conventionallens, which deploys by elastic recovery. A SMP phakic lens may also bedesigned to deploy in the anterior chamber for placement behind the irisplane during deployment. With current phakic IOL technology, if placedbehind the iris, there is a known higher incidence of cataractformation. This incidence can be reduced or eliminated with slowtailored deployment and positioning of an SMP lens.

Intracorneal Implants

Intracorneal implant devices have not achieved great success in thenational and international markets due to several limitations whichinclude: (a) difficulty with implantation; (b) requirement for largeincisions in the cornea to accommodate current devices; (c) inability tocorrect “refractive surprises” without returning to the procedure oroperating room; and (d) limitation in geometrical configurations ofcurrent devices due to inherent material properties. In contrast, SMPintracorneal implants may be designed to leverage the benefits of thecompressibility and deformability of SMP materials. A laser or blade isused to make an intracorneal incision, tunnel, and pocket to deliver theintracorneal implant. One of the current challenges is the severe traumaoften seen to the corneal tissues during insertion of these devices. A“tight fit” is needed as well as an adequate intracorneal passageway toadvance the intracorneal implant. The intracorneal implants are designedto be small enough to atraumatically be passed through a cornealincision and into the desired pocket. Then, the thermomechanicaldeployment and decompression of the implant occurs allowing for a securepositioning of the implant.

Extrusion and displacement of the intracorneal implants may be decreasedwith the SMP technology as well as decreasing infection rates because ofthe minimization of corneal trauma as well as the presence of a smallerincision, tunnel, and pocket. Advantages of using SMP materials forintracorneal implants compared to traditional devices may include theability to implant devices through minimally invasive approaches (e.g.,through incisions created by femtosecond lasers) with subsequent shapechange achieving larger device diameters for refractive correction.Another advantage is the ability to change the shape and size of SMPintracorneal implant devices post implantation in the cornea, forexample, if a “refractive surprise” occurs or if further changes inrefractive correction are needed. This can be achieved by constructingthe intracorneal implants with different material formulas in differentareas to provide differing Tg and refractive index values for each ofthe areas as described above with respect to SMP IOLs. A furtheradvantage is the ability to implant the devices in a more “rubbery”state, thus causing less trauma to the stromal tissue of the cornea.

Shape Memory Polymer Intraocalar Compression and Packaging

FIGS. 8A-13 depict exemplary steps in a process to deform a SMP IOL intoa compressed shape for packaging and implantation, at which point theSMP IOL will deploy and expand to return to its permanent shape with anextremely high degree of shape fixity. FIGS. 8A and 8D depict anexemplary, generic SMP intraocular lens 100. The SMP IOL 100 has acenter optic 102 and haptics 104 extending symmetrically from opposingsides of the optic 102. Each of the haptics 104 may be formed insections including a shoulder 106 connected with the optic 102, an arm108, and a terminal end 110. Upon deployment, the haptics 104 unfurlfrom their rolled and compressed conditions to press the terminal ends110 against the tissue forming the cavity of implantation to secure theoptic in an appropriate position.

The SMP IOL is formed by injection molding one of the formulationsdescribed above. In an exemplary implementation, an 80-20 (tBA-PEGDMA550) combination is used to create a 6 mm diameter optic 102 withextending haptics 104. The tBA-PEGDMA 550 mixture has extremely lowviscosity when heated in the mold and is thus able to easily flowthrough and fill the mold to form the very small diameter haptics 104.In another exemplary implementation, a combination of tBA (78%) andPEGDMA 1000 (22%), with or without a UV blocker BTA (0.5-1.0%) (e.g.,SMP106, SMP122, and SMP123, respectively) may be used to create theoptic 100. These formulas similarly have extremely low viscosities. In acast process molding, the mold may be oversized by 0.1-20% to accountfor a 5-20% volume shrinkage that typically occurs for these polymerchemistries during the polymerization process. In a liquid injectionmolding process, ultra-high pressures (e.g., >500-40,000 psi) may beutilized to minimize volume shrinkage as much as possible duringpolymerization. In addition, the combination of injection molding withpre-polymization techniques may be implemented to further minimizevolume shrinkage during the polymerization process.

In one implementation, the cure temperature and de-molding temperaturemay be the same to avoid thermal cycling. Alternatively, the mold may becooled to an optimal de-mold temperature where the material exhibits thegreatest robustness, typically somewhere slightly (e.g., 8° C.) belowTg. Once released from the mold, the SMP IOL 100 is in its permanentform. However, for implantation, it is desirable to reduce the size andform factor of the SMP IOL 100 such that it can be implanted through asmaller incision.

FIGS. 9A and 9B schematically depict a first step in the deformationprocess for the SMP IOL 202 to package the SMP IOL 202 into a deformedshape for storage and ultimately implantation. A rolling die 204defining a longitudinal channel 206 therein may be used to initiallyroll the SMP IOL 202. The SMP IOL 202 is placed over the channeloriented with the haptics extending across the channel as well. Atension wire 208 is placed parallel to and directly above the channel206 over the SMP IOL 202 while the ends of the tension wire 208 areposition coaxially with the longitudinal center of the channel 206. Therolling die 204 and SMP IOL 202 are then heated to approximately Tg. Thetension on the wire 208 is increased, drawing the entire length of thetension wire 208 into the channel 206 the tension wire is coaxial withthe longitudinal center of the channel. The tension wire 208 therebypushes the SMP IOL 202 within the channel 206, folding the SMP IOL 202in half around the tension wire 208 and deforming the SMP IOL 202 into aU-shape 202′ as shown in FIG. 9B. A first side of the U-shaped SMP IOL202′ (labeled “b” in FIG. 2B) is folded over the wire 208 in the channel206. Then a second side of the U-shaped SMP IOL 202′ (labeled “c” inFIG. 9B) is folded over the first side about the wire 208. The tensionwire 208 can then be removed. In one exemplary embodiment, the channelmay be 1.8 mm wide by 2.0 mm deep resulting in an SMP IOL 202′ that hasmaximum diametrical dimensions of 1.8 mm by 2.0 mm.

As depicted in FIG. 10A, the rolled SMP IOL 302 is next cooled below Tgwhile remaining within the channel 306 in the rolling die 304. Thecooling of the SMP IOL 302 while in the die channel locks the SMP IOL302 in the rolled configuration. The SMP IOL 302 can then be removedfrom the channel 306 in the rolling die 304 and will maintain its rolledshape as shown in FIG. 10B.

The rolled SMP IOL 402 is next placed within a fabric sheath or sock 404as shown in FIG. 11 for transmission of the rolled SMP IOL 402 through acompression die. The fabric sock 404 may be closed at one end and openat an opposite end and sized to fit snugly around the rolled SMP IOL402. The fabric sock 404 may be significantly longer than the length ofthe rolled SMP IOL 402 in order to assist in pulling the SMP IOL 402through a compression die. In an exemplary implementation, the fabricsock 404 may be made of a silk fabric.

FIGS. 12A and 12B depict the SMP IOL 402 in the fabric sock 404 beingpulled through a compression die 502. The compression die 502 defines aborehole 508 extending laterally therethrough from an entrance side 504to and exit side 506. The borehole 508 in the compression die 502 may bedivided into several sections of varying diameter. An entrance section510 opening up to the entrance side 504 may be of a constant diameter ofslightly larger than the diameter of the rolled SMP IOL 402 such thatthe SMP IOL 402 can be easily inserted into the borehole 508 of thecompression die 502. A middle section 512 of the borehole 508 tapers indiameter from the diameter of the entrance section 510 to a smallerdiameter that transitions into and is congruent with a diameter of anexit section 514 that opens the exit side 506. Continuing with theexemplary embodiment described above wherein the maximum diameter of therolled SMP IOL 402 is 2.0 mm, the diameter w of the entrance section 510may be formed as 2.0 mm or slightly greater. The middle section 512 maythen transition from 2.0 mm to 1.5 mm in diameter, and the diameter w′of the exit section may be a constant 1.5 mm in diameter.

As shown in FIGS. 12A and 12B, the open end of the fabric sock 404 isplaced within the borehole 508 from the entrance side 504 and is longenough to extend the length of the borehole 508 and extend out of theexit side 506. The open end of the fabric sock 404 may then be graspedto pull the rolled SMP IOL 402 within the fabric sock 404 into theentrance section 510 of the borehole 508. The compression die 502 isheated to a temperature greater than Tg for the SMP formulation useduntil the SMP IOL 402 reaches a temperature greater than Tg and issoftened. The fabric sock 404 is then pulled through the borehole 508whereby the rolled SMP IOL 402 is likewise pulled through the middlesection 512 and radially compressed. The compressed SMP IOL 402′ is thenleft in the reduced diameter exit section 514 while the compression dieand the compressed SMP IOL 402 therein are cooled to a temperature belowTg, thereby locking the compressed SMP IOL 402′ in the compressed state.Once the compressed SMP IOL 402′ has been cooled below Tg, it can beremoved from the compression die 502 and the fabric sock 404 and willremain in the compressed shape with a maximum diameter of w′ forpackaging, storage, and ultimately implantation as indicated in FIG. 13.

In an exemplary experiment, an SMP IOL with a 6 mm diameter optic wasrolled and compressed to a final diameter, w′, of 1.5 mm. The compressedSMP IOL was loaded into a 15 gauge hypodermic tube. The compressed SMPIOL in the tube was then introduced into a heated water bath at bodytemperature. A rod was inserted within the hypodermic tube to push theIOL out the end of the tube and deliver it into the water bath. Once inthe water bath, the SMP IOL expanded and unfurled to return to itsoriginal form with a 6 mm diameter optic with >98% accuracy in size andform.

Another exemplary implementation of a device and method for folding theIOL is depicted schematically in FIGS. 14A-14C. FIG. 14A depicts a firststep in the deformation process for an SMP IOL 702 to package the SMPIOL 702 into a deformed shape for storage and ultimately implantation. Arolling die 710 is formed with a pair of parallel walls 704 extendingabove a top surface of the die 710 to define a longitudinal channel 706therein. The base of the channel 706 may be arcuate or semicircular incross section in order to aid in the folding and achieve a relativelycylindrical SMP IOL 702 in the final compressed form. The SMP IOL 702 isplaced on the walls 704 over the channel 706 and oriented with thehaptics extending across the channel 706 as well. The rolling die 710and SMP IOL 702 are then heated to approximately Tg. The lateral edgesof the SMP IOL 702 may then be folded over within the channel 706between the walls 704 to form a rolled shape similar to theconfiguration of the IOL 302 in FIG. 10B. In one implementation, the IOL702 may be folded by hand using a tweezers or forceps. In anotherimplementation, a tension wire as described with respect to FIGS. 9A and9B may be used to depress the IOL 702 into the channel 706. In oneexemplary embodiment, the channel 706 may be 1.8 mm wide by 2.0 mm deepresulting in an SMP IOL 702 that has maximum diametrical dimensions of1.8 mm by 2.0 mm.

FIG. 14B depicts a second component of the deformation device, a secondcompression die 720 that works in cooperation with the roll die 710 tofurther compress the IOL 702. A pair of parallel channels 728 are formedwithin a top surface of the compression die 720 that are complementaryto or slightly larger in size (i.e., length, width, and depth) than thesize of the walls 704 (i.e., length, width, and height) of the rollingdie 710. A recessed wall 724 is thus formed within the top surface ofthe compression die 720 that separates and defines the channels 728. Therecessed wall 724 may thus be of a complementary width to or slightlysmaller in width than the channel 706 on the rolling die 710. The topsurface of the recessed wall 724 may further define a shallow trough 726with a curved or semi-circular cross section. The compression die 720may further be formed with one or more fluid channels 722 with inlet andoutlet fittings in order to maintain the compression die 720 at or abovethe Tg of the SMP IOL 702.

Once the SMP IOL 702 is rolled in the channel 706 of the rolling die710, the rolling die 710 is inverted and placed on top of thecompression die 720. The walls 704 of the rolling die 710 fit within thechannels 728 of the compression die 720. The recessed wall 724 of thecompression die 720 extends into the channel 706 of the rolling die 710and the trough 726 contacts the SMP IOL 702 within the channel 706. Therolling die 710 and the compression die 720 are then pressed togetherand the SMP IOL 702 is further compressed in size when measured incross-sectional diameter (however, the SMP IOL may increase in axiallength slightly when under radial compression between the rolling die710 and the compression die 720).

As shown in FIG. 14 C, since the depth of the parallel channels 728within the compression die 720 is slightly larger than the height of theparallel walls 704 on the rolling die 710, the top surface of therolling die 710 and the top surface of the compression die 720 reach aninterface and halt the compression of the SMP IOL 702. The depth of thetrough 726 and the depth of the channel 706 are chosen to define aseparation distance between the base of the channel 706 and the base ofthe trough 726 that corresponds to a desired final diameter of thecompressed SMP IOL 702. In an exemplary experiment, an SMP IOL with a 6mm diameter optic was compressed using this method to a final diameterof 1.6 mm. The compressed SMP IOL can then be loaded into an injectiontool for ab interno delivery.

In another exemplary implementation, an SMP IOL folded by this techniquemay be loaded into a lens injector for implantation. In an exemplary IOLplacement, a small incision may be made at the corneal limbus with ablade or laser and the tip of the injector may be inserted into theanterior chamber. Because of the slow deployment of the SMP IOL, thesurgeon can place the haptics and the optic in the correct locationduring lens deployment to avoid extensive manipulation of the SMP IOLafter full deployment. In addition, cataract extraction and lensimplantation can be performed with a smaller anterior capsularopening—as small as less than 1.8 mm in diameter. A smaller capsularopening with less disruption of the anterior capsule will increase theaccommodative ability of the implanted lens as the physiology ofaccommodation is less disrupted.

In one exemplary implementation, the injector tip may be placed throughthe cornea incision, across the anterior chamber, into the smallanterior capsular opening. The lens may be injected directly into thecapsular bag and slowly deploy without significant trauma to the lenscapsule. This is not possible with rapid deployment of known expandinglenses which often leads to capsular tears. Similarly a sulcus SMP IOLwill be supported in the ciliary sulcus with gentle pressure andapposition of the haptics to the ciliary sulcus structures. Further, ananterior chamber SMP IOL will be supported by the anterior chamber anglestructures with gentle pressure and apposition of the haptics to theanterior chamber angle structures. The slow, gradual deployment of anSMP IOL will significantly reduce the trauma to these tissue structuresas compared to the rapid, elastic deployment of present IOL materials.

All directional references (e.g., proximal, distal, upper, lower,upward, downward, left, right, lateral, longitudinal, front, back, top,bottom, above, below, vertical, horizontal, radial, axial, clockwise,and counterclockwise) are only used for identification purposes to aidthe reader's understanding of the present invention, and do not createlimitations, particularly as to the position, orientation, or use of theinvention. Connection references (e.g., attached, coupled, connected,and joined) are to be construed broadly and may include intermediatemembers between a collection of elements and relative movement betweenelements unless otherwise indicated. As such, connection references donot necessarily infer that two elements are directly connected and infixed relation to each other. The exemplary drawings are for purposes ofillustration only and the dimensions, positions, order and relativesizes reflected in the drawings attached hereto may vary.

The above specification, examples and data provide a completedescription of the structure and use of exemplary embodiments of theinvention as defined in the claims. Although various embodiments of theclaimed invention have been described above with a certain degree ofparticularity, or with reference to one or more individual embodiments,those skilled in the art could make numerous alterations to thedisclosed embodiments without departing from the spirit or scope of theclaimed invention. Other embodiments are therefore contemplated. It isintended that all matter contained in the above description and shown inthe accompanying drawings shall be interpreted as illustrative only ofparticular embodiments and not limiting. Changes in detail or structuremay be made without departing from the basic elements of the inventionas defined in the following claims.

The terms “comprise(s),” “include(s),” “having,” “has,” “can,”“contain(s),” and variants thereof, as used herein, are intended to beopen-ended transitional phrases, terms, or words that do not precludethe possibility of additional acts or structures. The present disclosurealso contemplates other embodiments “comprising,” “consisting of” and“consisting essentially of,” the embodiments or elements presentedherein, whether explicitly set forth or not.

1.-39. (canceled)
 40. A method of manufacturing an intraocular devicecomprising providing a shape memory polymer (SMP) material with a Tg;forming the SMP material in a permanent intraocular device form;mechanically compressing the intraocular device at a temperature aboveTg to deform the intraocular device into a smaller volume; and coolingthe deformed intraocular device while still in compression to atemperature below Tg to thereby create a stable deformed intraoculardevice with a delivery profile allowing for insertion through anincision of 2 mm or less, wherein the SMP material is selected from thegroup consisting of: (a) a SMP material comprising a tert-butyl acrylate(tBA) monomer and a bisphenol A propoxylate diacrylate (BPA-P)diacrylate cross-linking polymer, (b) a SMP material comprising atert-butyl acrylate (tBA) monomer and 10 wt % to 50 wt % of apoly(ethylene glycol) dimethacrylate cross-linking polymer with amolecular weight substantially between 500 and 2000, inclusive; (c) aSMP material comprising a tert-butyl acrylate (tBA) monomer and 10 wt %to 50 wt % of a poly(ethylene glycol) diacrylate crosslinking polymerwith a molecular weight substantially between 500 and 2000, inclusive;and (d) a SMP material comprising a tert-butyl acrylate monomer, anisobutyl acrylate monomer, a butyl acrylate monomer, and a poly(ethyleneglycol) dimethacrylate and/or a poly(ethylene glycol) diacrylatecross-linking monomer with a molecular weight substantially between 500and 2000, inclusive.
 41. The method of claim 40, wherein the formingoperation further comprises cast molding the SMP material into thepermanent intraocular device form.
 42. The method of claim 41, furthercomprising oversizing a mold by 0.1-20% of a desired final size of thepermanent intraocular device form to account for volume shrinkage thatmay occur during a polymerization process of the SMP material in thecast molding operation.
 43. The method of claim 40, wherein the formingoperation further comprises liquid injection molding the SMP materialinto the permanent intraocular device form.
 44. The method of claim 43,further comprising utilizing ultra-high pressures during the liquidinjection molding operation to minimize volume shrinkage duringpolymerization.
 45. The method of claim 40, wherein the formingoperation further comprises cryolathing the SMP material into thepermanent intraocular device form.
 46. The method of claim 40, whereinthe delivery profile of the deformed intraocular device is configured tofit within an incision less than or equal to 1.8 mm wide.
 47. The methodof claim 40 further comprising rolling the intraocular device at atemperature above Tg of the SMP material; cooling the rolled intraoculardevice while still in a rolled form to a temperature below Tg to therebycreate a stable rolled intraocular device; and mechanically compressingthe intraocular device to a diameter of less than or equal to 1.8 mm.48. The method of claim 40 further comprising rolling the intraoculardevice at a temperature above Tg of the SMP material; and radiallycompressing the intraocular device within a die to a diameter of lessthan or equal to 1.8 mm while maintaining the temperature above Tg. 49.The method of claim 40 further comprising packaging the deformedintraocular device for storage at or above room temperature.
 50. Themethod of claim 40, wherein the intraocular device is an intraocularlens.
 51. The method of claim 40, wherein the intraocular device is anintracorneal implant.
 52. The method of claim 40, wherein the SMPmaterial comprises a tert-butyl acrylate (tBA) monomer and a bisphenol Apropoxylate diacrylate (BPA-P) diacrylate cross-linking polymer.
 53. Themethod of claim 40, wherein the SMP material comprises a tert-butylacrylate (tBA) monomer and 10 wt % to 50 wt % of a poly(ethylene glycol)dimethacrylate cross-linking polymer with a molecular weightsubstantially between 500 and 2000, inclusive.
 54. The method of claim40, wherein the SMP material comprises a tert-butyl acrylate (tBA)monomer and 10 wt % to 50 wt % of a poly(ethylene glycol) diacrylatecrosslinking polymer with a molecular weight substantially between 500and 2000, inclusive.
 55. The method of claim 40, wherein the SMPmaterial comprises a tert-butyl acrylate monomer, an isobutyl acrylatemonomer, a butyl acrylate monomer, and a poly(ethylene glycol)dimethacrylate and/or a poly(ethylene glycol) diacrylate cross-linkingmonomer with a molecular weight substantially between 500 and 2000,inclusive.
 56. The method of claim 55, wherein the Tg of the SMPmaterial is between 10° C. and 60° C.
 57. The method of claim 40,wherein the Tg of the SMP material is greater than or equal to humanbody temperature.
 58. The method of claim 40, wherein the intraoculardevice once implanted and reformed exhibits greater than 98 percentshape recovery from the deformed intraocular device to upon reaction toan external stimulus.
 59. The method of claim 58 wherein the externalstimulus is heat above Tg.
 60. The method of claim 59, wherein Tg issubstantially equal to 37° C.
 61. The method of claim 58, wherein theexternal stimulus is ultraviolet radiation.
 62. The method of claim 58,wherein the reaction to the external stimulus is delayed for up to 600seconds.
 63. The method of claim 58, wherein the reaction initiateswithin 3 to 25 seconds.
 64. The method of claim 40, wherein the SMPmaterial comprises a color additive.